RARE DISEASE
Bardet-Biedl syndrome
Bardet-Biedl syndrome
Bardet-Biedl syndrome
Synonyms: BBS
Synonyms: BBS
Synonyms: BBS
Drug discovery
5
drugs
With orphan designations
Overview
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by rod-cone dystrophy, obesity, polydactyly, renal anomalies, learning disabilities, and hypogonadism. Caused by mutations in at least 24 genes affecting cilia function, it leads to multisystemic complications. Diagnosis relies on clinical criteria (four major features or three major plus two minor). Management requires a multidisciplinary approach addressing metabolic, renal, and visual impairments, with emerging therapies targeting underlying genetic mechanisms [1][5][12].
Burden
Leading morbidity: progressive vision loss, renal failure (30–50% develop chronic kidney disease), and obesity-related complications (e.g., type 2 diabetes) [1][5][12].
Caregiver burden: 53% of total costs stem from hyperphagia/obesity management, productivity loss, and emotional strain [4][9].
Lifetime societal cost: ~$5.2 million per patient, driven by medical care, reduced QALYs, and premature mortality [4][9].
Therapies
Categories: rare abdominal surgical diseases, rare developmental anomalies during embryogenesis, rare endocrine diseases, rare gastroenterological diseases, rare genetic diseases, rare gynecological and obstetric diseases, rare infertility disorders, rare neurological diseases, rare ophthalmic disorders, rare renal diseases, rare transplant-related disorders
Research Papers
251 drug discovery papers about Bardet-Biedl syndrome, with 1 first-in-class and 14 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
251 drug discovery papers about Bardet-Biedl syndrome, with 1 first-in-class and 14 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2025-10-17 | Effect of Tirzepatide in an Adolescent With Early-Onset Obesity, Hyperphagia, and Type 2 Diabetes
Early-onset severe obesity is rare and largely treatment-resistant to standard measures. Etiologies include syndromic disorders (Prader-Willi, Bardet-Biedl and Alström syndromes), monogenic defects of appetite-regulating pathways - most significantly melanocortin-4-receptor (MC4R) deficiency, but also leptin receptor (LEPR), pro-opiomelanocortin (POMC), and secondary hypothalamic injury, most commonly craniopharyngiomas. Most childhood obesity, however, is polygenic, arising from interactions of environmental and genetic factors. In many patients, no clear etiology is identified. Treatment remains challenging, particularly if hyperphagia and reduced satiety are predominant presenting features. We describe the case of a 19-year-old male with a history of autism spectrum disorder, attention-deficit hyperactivity disorder (ADHD), type 2 diabetes mellitus (T2DM) and morbid obesity, who showed a clinically significant response to tirzepatide therapy following failed conventional interventions. This case highlights the potential role of dual incretin therapy in adolescents with severe early-onset obesity and hyperphagia, even in the absence (based on present knowledge) of identifiable hypothalamic or genetic pathology.
2025-10-15 | Efficacy of Semaglutide in Pediatric Patients With Bardet-Biedl Syndrome and Alström Syndrome
Abstract Bardet-Biedl syndrome (BBS) and Alström syndrome (AS) are rare autosomal recessive ciliopathies characterized by severe multisystemic involvement, including metabolic, sensory, and developmental impairments. Both conditions result from primary cilia dysfunction, disrupting pathways such as leptin and insulin signaling, which leads to obesity and insulin resistance. While setmelanotide, a melanocortin-4 receptor agonist, may be an effective therapy for obesity in these conditions (especially BBS), its cost limits accessibility for many patients. We describe two pediatric cases (one with BBS and another with AS) demonstrating significant metabolic improvements with semaglutide, a glucagon-like peptide-1 receptor agonist. These observations suggest that some cases of BBS and AS may be treated with semaglutide.
2025-09-01 | OC29 - Genotype over phenotype: the road less travelled in diagnosing Bardet- Biedl syndrome
Abstract Introduction Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive disorder classified under ciliopathies. It typically presents with a combination of features such as retinal dystrophy, polydactyly, renal abnormalities, hypogonadism, intellectual disability, and obesity. While obesity is a hallmark feature, its occurrence in isolation—without other classical manifestations—is uncommon. With advancements in molecular diagnostics, atypical presentations of BBS are being increasingly identified. Purpose This case report highlights a rare phenotype of BBS, where metabolic abnormalities appeared in the absence of traditional clinical signs. Case Summary A 19-year-old male presented with progressive weight gain beginning at age 5. At the time of evaluation, he weighed 135 kg and had a blood pressure of 158/108 mmHg. Clinical examination revealed acanthosis nigricans and multiple skin tags. Notably, he lacked typical BBS features such as polydactyly, retinal dystrophy, genital anomalies, or cognitive impairment. He had normal neurodevelopment and reported no visual issues. Given the early-onset severe obesity and metabolic features, genetic testing was pursued, which identified a pathogenic mutation in the IFT172 gene—associated with BBS20. This confirmed the diagnosis despite the absence of classical clinical features. Treatment and Follow-up Following genetic confirmation and absence of retinal involvement, the patient was initiated on lifestyle modification and oral semaglutide, starting at 3 mg daily with uptitration to 7 mg over six months. Follow-up at 3 months showed a weight reduction of 10 kg, and by 6 months, a total weight loss of 20 kg was achieved. The treatment was well tolerated with a favorable safety profile. Conclusion This case underscores a mild, atypical presentation of Bardet-Biedl Syndrome, manifesting solely with obesity and features of metabolic syndrome. It emphasizes the critical role of genetic testing in evaluating individuals with early- onset obesity, especially when phenotypic hallmarks are absent. Early diagnosis facilitates timely intervention, genetic counselling, and longitudinal monitoring, as additional features of BBS may develop over time.The positive metabolic response to semaglutide underscores its therapeutic potential in syndromic obesity, even in the absence of classical phenotypic markers.
2025-06-24 | Sudden acquired retinal degeneration syndrome may be an acquired primary ciliopathy, phenotypically similar to human Alström and Bardet-Biedl syndromes.
Sudden acquired retinal degeneration syndrome (SARDS) is an acquired canine disease that presents as rapidly progressive retinal degeneration, often accompanied by polyphagia, weight gain, polydipsia, polyuria, and hyposmia. Alström syndrome (AS) and Bardet-Biedl syndrome (BBS) are rare human autosomal recessive genetic disorders marked by progressive retinopathy, polyphagia, obesity, polydipsia, polyuria, and hyposmia, with varying degrees of phenotypic severity. While the etiology of AS and BBS is partially understood, the cause of acquired SARDS remains elusive. Historically, scientific inquiry has focused on an immunologic insult and/or endocrinopathy as the cause of SARDS. Clinicians have often pointed to these Cushingoid symptoms mentioned above in SARDS patients as evidence of a contributing endocrinopathy. However, systemic cortisol concentrations, both pre- and post-ACTH stimulation, typically do not differ appreciably between normal patients and those with SARDS. Blindness due to photoreceptor degeneration, along with the observed Cushingoid symptoms, may result from dysfunctional or absent primary cilia, as documented in human AS and BBS cases. Recognizing SARDS as a possible acquired ciliopathy may be the first step toward seeking effective treatments.
2025-06-16 | Should GLP-1 receptor agonist therapy be used to treat obesity in Bardet-Biedl syndrome?
Bardet-Biedl syndrome (BBS) is a complex genetic condition that can affect multiple organ systems, frequently causing pigmentary retinopathy, renal abnormalities, polydactyly, and obesity. Metabolic disturbances including obesity, unsuppressed appetite, and an increased risk of type 2 diabetes (T2D) present clinical management challenges. In this issue of the JCI, Singh et al. present a mouse model of a specific BBS subtype with genetic deletion of the Bbs5 gene. The model recapitulates many of the clinical features observed in patients living with BBS5 and sheds light on adipocyte biology, as well as the hypothalamic mechanisms driving hunger- and food-seeking behaviors that fuel the adverse metabolic phenotype. Importantly, exogenous GLP-1 receptor agonist treatment suppressed both appetite and weight, opening opportunities for direct translation into the clinical setting.
small molecules
2026-09-28 | Ciliary Membrane Lipid Homeostasis in Health and Disease
The ciliary membrane is an active, highly specialized lipid landscape that dictates ciliary identity and function. Distinct from the surrounding plasma membrane, it exhibits a tailored lipid architecture-enriched in specific phosphoinositides, cholesterol, and sphingolipids-that shapes membrane curvature and establishes spatial platforms for signaling cascades. Emerging evidence indicates that disrupting the lipid microenvironment gives rise to a distinct spectrum of ciliopathies, driven by mislocalized signaling receptors, impaired intraflagellar transport (IFT), and disintegrated inner structures. This review bridges biophysical membrane dynamics with genetic pathology, positioning ciliary lipids not merely as structural components, but as active orchestrators of ciliary gatekeeping, cilia motility, and cilia signal transduction. By remapping the molecular mechanics of lipid dysregulation in diseases such as Bardet-Biedl syndromes, we highlight how targeting the ciliary lipidome opens new therapeutic avenues for human ciliopathies.
2026-09-16 | BBS10 ‑related Bardet‑Biedl syndrome with an atypical presentation of diabetes mellitus: A case report
Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive ciliopathy characterized by extensive clinical heterogeneity, which often complicates its diagnosis.The present study reported the case of a 31-year-old woman who presented with longstanding, poorly controlled type 2 diabetes mellitus and its associated complications.The patient exhibited classic features including Class I obesity, retinal dystrophy, postaxial polydactyly, renal dysfunction and hypergonadotropic hypogonadism.A definitive diagnosis was established through whole-exome sequencing, which identified compound heterozygous pathogenic variants in the BBS10 gene (a nonsense mutation, p.Arg256 * and a missense mutation, p.Gly180Glu).This case is novel in presenting with adult-onset diabetes as the primary complaint, highlighting the necessity of including BBS in the differential diagnosis of patients with early-onset metabolic disorders and multisystem involvement.Of note, the patient's glycemic control improved after treatment with a glucagon-like peptide-1 receptor agonist (semaglutide).This observation provides important longitudinal evidence suggesting a promising therapeutic strategy for managing metabolic dysfunction in BBS, potentially by engaging residual G-protein-coupled receptor signaling pathways despite underlying ciliary defects.
2026-09-15 | Setmelanotide Response Variability in Two Genetically Confirmed Pediatric Kidney Transplant Recipients with Bardet-Biedl Syndrome.
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy associated with hyperphagic obesity and kidney disease. Evidence on setmelanotide after pediatric kidney transplantation is limited. We evaluated two children with BBS treated with setmelanotide after kidney transplantation, collecting anthropometric, hunger, metabolic, graft-function, cyclosporine and genetic data. Patient 1, a 17-year-old boy with a homozygous pathogenic SDCCAG8 exon deletion, improved over 12 months: weight 55.6 to 48.0 kg, BMI 26.6 to 23.0 kg/m2, BMI-for-age z-score +1.60 to +0.43, maximal-hunger score 8/10 to 5/10, and HbA1c 6.5% to 5.1%. Patient 2, an 8-year-old girl with a homozygous likely pathogenic BBS5 splice-site variant and a heterozygous PCSK1 N221D variant, showed reduced hunger and an initial z-score fall from +6.10 to +5.69 by month 2.5, meeting the 0.2-point threshold for clinically meaningful change; this was not sustained, and BMI rose from 38.0 to 42.7 kg/m2 by eight months despite a dose of 3 mg/day. Graft function and cyclosporine trough concentrations remained stable, and skin hyperpigmentation was the only treatment-related adverse effect. In these two patients, setmelanotide was not associated with graft deterioration or altered cyclosporine trough concentrations, although two cases cannot establish safety. The divergent trajectories highlight interindividual variability; the role of PCSK1 N221D remains uncertain, and these observations are hypothesis-generating.
2026-09-15 | Sequential liraglutide and setmelanotide therapy in Bardet-Biedl Syndrome: metabolic and renal outcomes in a real-world case report and literature review.
Bardet-Biedl syndrome (BBS) is a syndromic ciliopathy characterized by multiple clinical features, including obesity and kidney disease. Therapeutic options remain limited. Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is approved for obesity in BBS, but real-world data in adults is scarce. This case highlights the synergistic metabolic and nephroprotective effects of a sequential therapeutic strategy combining a glucagon-like peptide-1 (GLP-1) receptor agonist and a MC4R agonist. We report the case of a 37-year-old male with genetically confirmed BBS due to compound heterozygous likely pathogenic BBS10 variants presenting with obesity, insulin resistance, dyslipidemia, albuminuria and metabolic dysfunction-associated steatotic liver disease (MASLD). Treatment with liraglutide induced modest weight loss (-3.4%, BMI 35.2→34 kg/m²), improved urinary albumin-to-creatinine ratio (uACR) and liver enzymes levels within 8 months. Following discontinuation of liraglutide, setmelanotide therapy was subsequently initiated. After 12 months of treatment, the patient achieved a 10.5% weight loss compared with baseline (BMI 35.2→31.5 kg/m²), normalization of liver transaminases, reduced liver stiffness, and sustained improvement in uACR, while eGFR remained stable. Fasting insulin and HOMA-IR improved. Metformin, statin, and fenofibrate were discontinued, though fenofibrate was later reintroduced for hypertriglyceridemia. Two interventional studies (n≃10-40, 3-52 weeks) similarly reported consistent reduction in metabolic syndrome burden (METs-Z-BMI-score), liver steatosis, stiffness, and enzymes, while renal biomarkers showed stabilization or improvement, supporting potential hepatoprotective and reno-protective effects. Setmelanotide promoted clinically meaningful weight loss and improved liver, kidney, and metabolic parameters in an adult patient carrying BBS10-likely pathogenic variants. Together with emerging evidence for interventional studies, these findings suggest that MC4R agonism may confer organ-level and cardiometabolic benefits beyond weight reduction.
2026-09-11 | Supplemental Material for: Sequential liraglutide and setmelanotide therapy in Bardet-Biedl Syndrome: metabolic and renal outcomes in a real-world case report and literature review
IntroductionBardet–Biedl syndrome (BBS) is a syndromic ciliopathy characterized by multiple clinical features, including obesity and kidney disease.Therapeutic options remain limited. Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is approved for obesity in BBS, but real-world data in adults is scarce. This case highlights the synergistic metabolic and nephroprotective effects of a sequentialtherapeutic strategy combining a glucagon-like peptide-1 (GLP-1) receptor agonist and a MC4R agonist.Case PresentationWe report the case of a 37-year-old male with genetically confirmed BBS due to compound heterozygouslikelypathogenicBBS10 variants presenting with obesity, insulin resistance, dyslipidemia, albuminuria and metabolic dysfunction–associated steatotic liver disease (MASLD). Treatment with liraglutide induced modest weight loss (–3.4%, BMI 35.2→34 kg/m²), improved urinary albumin-to-creatinine ratio (uACR) and liver enzymes levels within 8 months.Following discontinuation of liraglutide, setmelanotide therapy wassubsequentlyinitiated. After 12 months of treatment, the patient achieved a 10.5% weight loss compared with baseline (BMI 35.2→31.5 kg/m²), normalization of liver transaminases, reduced liver stiffness, and sustained improvement in uACR, while eGFR remained stable. Fasting insulin and HOMA-IR improved. Metformin, statin, and fenofibrate were discontinued, though fenofibrate was later reintroduced for hypertriglyceridemia. Two interventional studies (n≃10–40, 3–52 weeks) similarly reported consistent reduction in metabolic syndrome burden (METs-Z-BMI-score), liver steatosis, stiffness, and enzymes, while renal biomarkers showed stabilization or improvement, supporting potential hepatoprotective and reno-protective effects. ConclusionSetmelanotide treatment was associated with clinically meaningful weight loss and improvements in liver, kidney, and metabolic parameters in this adult patient with BBS. This case supports the potential role of setmelanotide in the multidisciplinary management of BBS and highlights the need for further studies to better define its effects beyond weight reduction.
gene therapies
2026-08-14 | Clinical, Genetic, and Endocrine Features of Bardet-Biedl Syndrome in a Pediatric and Adult Cohort.
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder characterized by clinical and genetic heterogeneity. Data on the prevalence of clinical manifestations and comorbidities in BBS, particularly in pediatric patients, are limited. This study aimed to assess the prevalence and various manifestations of endocrine and other clinical comorbidities among pediatric and adult patients with BBS. This retrospective chart review included pediatric and adult patients with BBS evaluated at an academic tertiary care center in the United States between 2000 and 2024. The study included 31 patients (7 children and 24 adults) with seven identified pathogenic variants associated with BBS. The most common genetic etiology was biallelic variants in BBS1 (36%). Obesity was diagnosed in 86% of children and 100% of adults. No children had diabetes or prediabetes, whereas 46% of adults were affected. Dyslipidemia was identified in 29% of children and 46% of adults. No thyroid abnormalities were identified in children, whereas 25% of adults were affected. Retinal dystrophy was present in 71% of children and 96% of adults. Polydactyly was observed in 100% of children and 75% of adults. Chronic kidney disease was present in 29% of children and 63% of adults. This study highlights the clinical heterogeneity and substantial multisystem burden of BBS across pediatric and adult patients. The greater prevalence of diabetes/prediabetes, dyslipidemia, thyroid abnormalities, chronic kidney disease, and visual impairment among adults suggests that these complications may emerge or progress over time. Early recognition, proactive longitudinal surveillance, and comprehensive multidisciplinary care are essential to optimize management across the lifespan.
2026-01-19 | Retinal Degeneration and Visual Outcomes in Patients With Bardet-Biedl Syndrome: Genotypic Influences From a Caribbean Cohort.
Background The Bardet-Biedl syndrome (BBS) is a rare multisystem ciliopathy characterized by retinal degeneration, polydactyly, truncal obesity, hypogonadism, and hypogonadotropism. Progressive rod-cone dystrophy leads to early-onset vision loss. Despite increased genetic screening, BBS remains underdiagnosed in Caribbean populations. This study aims to describe the genetic and ocular phenotype of patients with BBS in Puerto Rico and explore genotype-phenotype correlations. Methods We conducted a retrospective chart review of 36 genetically confirmed BBS patients from a hereditary retinal disease clinic in Puerto Rico. Data collected included best-corrected visual acuity (BCVA), refractive error, visual field mean deviation (MD), and macular optical coherence tomography (OCT) measurements (volume and thickness). Genetic testing identified the BBS subtype and zygosity. Descriptive and statistical analyses were performed. The study was approved by a certified institutional review board (IRB). Results Age ranged from three to 69 years old. Mutations in the BBS1 gene were most frequent (86%), followed by BBS7 (8%), BBS10 (3%), and BBS19 (3%). Most patients had homozygous mutations in the BBS1 (%). The mean BCVA was 2.0 logMAR OD and 2.1 logMAR OS. Patients with homozygotic mutations in the BBS1 had worse vision than compound heterozygotes (p=0.025). Upon visual field examination, the MD was -27.6 dB OD and -28.3 dB OS. Near-absent visual fields occurred in patients with advanced disease. Macular volume and thickness averaged 8.2 mm³/227 µm (OD) and 7.7 mm³/216 µm (OS). Structural damage was associated with inner/outer segment disruption on OCT. Conclusions Mutations in the BBS1 are the most frequent in Puerto Rico, often associated with profound visual impairment and retinal thinning. These findings underscore the importance of early ophthalmic evaluation and genetic testing in patients with syndromic retinitis pigmentosa. Genotype-specific differences in visual decline support personalized surveillance and future therapeutic planning.
2025-11-02 | Bardet-Biedl Syndrome: Ocular Genetic Trials
Bardet-Biedl Syndrome is a rare genetic disorder with autosomal recessive inheritance that affects multiple organ systems. It is characterized by retinal dystrophy, obesity, polydactyly, renal anomalies, and cognitive impairment, this syndrome prominently involves ocular manifestations, which constitute one of the major sources of morbidity. In the majority of cases, progressive retinal degeneration begins in childhood or early adulthood, leading to significant vision loss. The molecular pathogenesis of BBS is associated with genetic mutations that disrupt the function of primary cilia. These mutations occur in genes encoding structural or regulatory components of the BBSome complex, which plays a crucial role in fundamental cellular processes such as cytoskeletal organization, protein trafficking, and intracellular signaling. In recent years, ocular genetic studies have expanded the spectrum of known mutations through functional analyses, while animal models have provided deeper insights into the molecular mechanisms underlying retinal pathology. From a therapeutic standpoint, gene replacement strategies have shown promising results at the preclinical level; however, the considerable genetic heterogeneity and the multisystemic nature of the syndrome pose challenges for the clinical translation of these approaches.
2025-10-29 | Clinical spectrum of Bardet-Biedl Syndrome: A case series
Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by a wide spectrum of clinical manifestations, including retinal dystrophy, obesity, post-axial polydactyly, learning disabilities, hypogonadism, and renal abnormalities. Early recognition is often challenging due to its gradual progression and overlapping features with other conditions, particularly in resource-limited settings where genetic testing is not readily available. We report a series of four Bangladeshi cases with variable phenotypic expressions of BBS. All patients presented with progressive visual impairment, obesity, and polydactyly, accompanied by additional features such as diabetes mellitus, dyslipidemia, hypogonadism, renal impairment, developmental delay, and behavioral disturbances. Diagnosis was established based on Beales’ clinical criteria, with patients meeting multiple primary and secondary features. Renal involvement was observed in two cases, including diabetic nephropathy and focal segmental glomerulosclerosis, underscoring its role as a major determinant of morbidity and mortality. Management required a multidisciplinary approach involving endocrinology, ophthalmology, nephrology, and mental health services, alongside lifestyle modification, pharmacotherapy, and family counseling. This case series highlights the clinical heterogeneity of BBS, the importance of heightened clinical suspicion for early detection, and the need for comprehensive multidisciplinary care to improve long-term outcomes in affected individuals. [J Assoc Clin Endocrinol Diabetol Bangladesh, 2025;4(Suppl 1): S49]
2025-09-02 | Atypical Retinitis Pigmentosa with Systemic Features in Bardet--Biedl Syndrome
Title:Atypical Retinitis Pigmentosa with Systemic Features in Bardet–Biedl SyndromeAuthor1-Muhammad Umar Ahsan, MBBS E-mail:umarahsan219@gmail.com Affiliation: D.G.Khan medical college, Dera Ghazi Khan, Pakistan ORCID: 0009-0008-0627-2521 2- Dr Saba S
cell therapies
2025-10-22 | Renal Transplant in a Bardet-Biedl Syndrome Patient: A First Case From Azerbaijan.
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by multisystem involvement, with renal pathology, including end-stage renal disease, being a major cause of morbidity and mortality. This case report presents a 14-year-old boy with BBS and end-stage renal disease who underwent a successful living donor kidney transplantation, marking the first reported case in Azerbaijan. Despite multiple comorbidities, including obesity, hypertension, and high panel reactive antibody levels, the patient achieved stable graft function with a rapid postoperative creatinine decline. Postoperative management focused on immunosuppression and lifestyle adjustments. This case contributes to the limited literature on BBS, highlighting both the challenges and favorable outcomes of renal transplantation in patients with this rare genetic disorder.
2013-04-01 | Proteomic Analysis of Human Blastocoel Fluid and Blastocyst Cells
Human embryonic stem cells (hESCs) are derived from the inner cell mass (ICM) of the blastocyst and can differentiate into any cell type in the human body. These cells hold a great potential for regenerative medicine, but to obtain enough cells needed for medical treatment, culture is required on a large scale. In the undifferentiated state, hESCs appear to possess an unlimited potential for proliferation, but optimal, defined, and safe culture conditions remain a challenge. The aim of the present study was to identify proteins in the natural environment of undifferentiated hESCs, namely, the blastocoel fluid, which is in contact with all the cells in the blastocyst, including hESCs. Fifty-three surplus human blastocysts were donated after informed consent, and blastocoel fluid was isolated by micromanipulation. Using highly sensitive nano-high-pressure liquid chromatography–tandem mass spectrometry, 286 proteins were identified in the blastocoel fluid and 1,307 proteins in the corresponding cells of the blastocyst. Forty-two were previously uncharacterized proteins—8 of these originated from the blastocoel fluid. Furthermore, several heat shock proteins (Hsp27, Hsp60, Hsc70, and Hsp90) were identified in blastocoel fluid together with zona pellucida proteins (ZP2–4), Vitamin D-binding protein, and Retinol-binding protein 4. Proteins that regulate ciliary assembly and function were also identified, including Bardet-Biedl syndrome protein 7. This study has identified numerous proteins that cells from the ICM of the human blastocyst are exposed to via the blastocoel fluid. These results can be an inspiration for the development of improved culture conditions for hESCs.
other
2025-11-24 | Splice-switching antisense oligonucleotides correct cryptic exon inclusion and restore SDCCAG8 protein in Bardet-Biedl Syndrome.
Bardet-Biedl Syndrome (BBS) is a ciliopathy often associated with progressive blindness and obesity. A patient presenting with BBS was discovered to have two mutations within 55bp of each other in intron 7 of SDCCAG8 (BBS16). One of the biallelic mutations, c.740+356C>T, causes inclusion of cryptic exon(s) containing premature termination codons, while c.740+301G>A has not been characterized. We hypothesized that antisense oligonucleotides (ASOs) complementary to the patient's mutations or to the cryptic exon splice sites would correct the splicing of SDCCAG8 between exons 7 and 8 to prevent cryptic exon inclusion and restore SDCCAG8 expression. We systematically screened 20nt-long ASOs tiled across each mutation and ASOs targeting the 3' splice sites of the cryptic exons in patient-derived fibroblasts, using RT-PCR assays to assess exon 7 and 8 splicing. We identified one ASO for each mutation and a cryptic exon-targeting ASO that restored the splicing pattern to that observed in an unaffected cell line. Lead ASOs were further investigated through RT-PCR, RNA sequencing, and western blotting to confirm ASO-mediated restoration of wild-type transcript and protein. Notably, ASO 20, which targets the cryptic exon 7a/7a' splice site rather than patient-specific mutations, achieved the greatest rescue effect, increasing exon 7-8 splicing from 0% to an average of 26% and restoring SDCCAG8 protein from undetectable levels to approximately 40% of wild-type expression. This mutation-agnostic approach could benefit multiple patients with cryptic exon inclusion in this region of SDCCAG8, expanding therapeutic impact beyond traditional N-of-1 ASO strategies. These findings establish a molecular foundation for clinical development of ASO therapy for BBS caused by SDCCAG8 splicing defects.
2025-07-28 | Analysis of the Body Mass Index of Latino Patients With Bardet-Biedl Syndrome.
Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive disorder characterized by multi-systemic manifestations, including truncal obesity, rod-cone dystrophy, polydactyly, and learning disabilities. The syndrome is associated with mutations in at least 28 genes, with BBS1 being the most common. This study investigates the correlation between body mass index (BMI) and specific genetic mutations in a cohort of 27 Latino patients with BBS. A chart review of 27 patients with BBS was conducted. Comprehensive ophthalmic evaluations, including best corrected visual acuity (BCVA), optical coherence tomography, and electroretinography, were performed. Genetic screening was conducted using next-generation sequencing with a focus on BBS1, BBS7, and BBS19 mutations. BMI was classified into normal, overweight, and obese categories. Statistical analyses (chi-square and Kruskal-Wallis test) were used to evaluate the data. The cohort had a mean age of 39 years, with 21 patients (77.8%) carrying mutations in the BBS1 gene. Among the cohort, a total of 14 patients (51.9%) were classified as obese, 10 (37.0%) as overweight, and three (11.1%) as normal weight. Obesity was most common in patients with BBS1 mutations, with 11 obese patients (78.6%) carrying BBS1 mutations, while patients with BBS7 and BBS19 mutations exhibited lower rates of obesity. Among obese patients, 10 (71.4%) were homozygous for mutations in the associated genes, and three (21.4%) were compound heterozygotes. Gender did not show statistically significant differences in obesity prevalence; however, male patients were more frequently overweight. This study confirms a strong association between BBS1 mutations and obesity in BBS patients, with homozygous and compound heterozygous mutations contributing to more severe clinical manifestations. Further research is required to better understand the genotype-phenotype relationship and to explore the role of environmental factors, such as physical activity, in modifying obesity outcomes. Larger, more diverse studies are needed to validate these findings and to develop targeted therapeutic strategies for BBS-related obesity.
proteins
2025-10-17 | Effect of Tirzepatide in an Adolescent With Early-Onset Obesity, Hyperphagia, and Type 2 Diabetes
Early-onset severe obesity is rare and largely treatment-resistant to standard measures. Etiologies include syndromic disorders (Prader-Willi, Bardet-Biedl and Alström syndromes), monogenic defects of appetite-regulating pathways - most significantly melanocortin-4-receptor (MC4R) deficiency, but also leptin receptor (LEPR), pro-opiomelanocortin (POMC), and secondary hypothalamic injury, most commonly craniopharyngiomas. Most childhood obesity, however, is polygenic, arising from interactions of environmental and genetic factors. In many patients, no clear etiology is identified. Treatment remains challenging, particularly if hyperphagia and reduced satiety are predominant presenting features. We describe the case of a 19-year-old male with a history of autism spectrum disorder, attention-deficit hyperactivity disorder (ADHD), type 2 diabetes mellitus (T2DM) and morbid obesity, who showed a clinically significant response to tirzepatide therapy following failed conventional interventions. This case highlights the potential role of dual incretin therapy in adolescents with severe early-onset obesity and hyperphagia, even in the absence (based on present knowledge) of identifiable hypothalamic or genetic pathology.
2025-10-15 | Efficacy of Semaglutide in Pediatric Patients With Bardet-Biedl Syndrome and Alström Syndrome
Abstract Bardet-Biedl syndrome (BBS) and Alström syndrome (AS) are rare autosomal recessive ciliopathies characterized by severe multisystemic involvement, including metabolic, sensory, and developmental impairments. Both conditions result from primary cilia dysfunction, disrupting pathways such as leptin and insulin signaling, which leads to obesity and insulin resistance. While setmelanotide, a melanocortin-4 receptor agonist, may be an effective therapy for obesity in these conditions (especially BBS), its cost limits accessibility for many patients. We describe two pediatric cases (one with BBS and another with AS) demonstrating significant metabolic improvements with semaglutide, a glucagon-like peptide-1 receptor agonist. These observations suggest that some cases of BBS and AS may be treated with semaglutide.
2025-09-01 | OC29 - Genotype over phenotype: the road less travelled in diagnosing Bardet- Biedl syndrome
Abstract Introduction Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive disorder classified under ciliopathies. It typically presents with a combination of features such as retinal dystrophy, polydactyly, renal abnormalities, hypogonadism, intellectual disability, and obesity. While obesity is a hallmark feature, its occurrence in isolation—without other classical manifestations—is uncommon. With advancements in molecular diagnostics, atypical presentations of BBS are being increasingly identified. Purpose This case report highlights a rare phenotype of BBS, where metabolic abnormalities appeared in the absence of traditional clinical signs. Case Summary A 19-year-old male presented with progressive weight gain beginning at age 5. At the time of evaluation, he weighed 135 kg and had a blood pressure of 158/108 mmHg. Clinical examination revealed acanthosis nigricans and multiple skin tags. Notably, he lacked typical BBS features such as polydactyly, retinal dystrophy, genital anomalies, or cognitive impairment. He had normal neurodevelopment and reported no visual issues. Given the early-onset severe obesity and metabolic features, genetic testing was pursued, which identified a pathogenic mutation in the IFT172 gene—associated with BBS20. This confirmed the diagnosis despite the absence of classical clinical features. Treatment and Follow-up Following genetic confirmation and absence of retinal involvement, the patient was initiated on lifestyle modification and oral semaglutide, starting at 3 mg daily with uptitration to 7 mg over six months. Follow-up at 3 months showed a weight reduction of 10 kg, and by 6 months, a total weight loss of 20 kg was achieved. The treatment was well tolerated with a favorable safety profile. Conclusion This case underscores a mild, atypical presentation of Bardet-Biedl Syndrome, manifesting solely with obesity and features of metabolic syndrome. It emphasizes the critical role of genetic testing in evaluating individuals with early- onset obesity, especially when phenotypic hallmarks are absent. Early diagnosis facilitates timely intervention, genetic counselling, and longitudinal monitoring, as additional features of BBS may develop over time.The positive metabolic response to semaglutide underscores its therapeutic potential in syndromic obesity, even in the absence of classical phenotypic markers.
2025-06-24 | Sudden acquired retinal degeneration syndrome may be an acquired primary ciliopathy, phenotypically similar to human Alström and Bardet-Biedl syndromes.
Sudden acquired retinal degeneration syndrome (SARDS) is an acquired canine disease that presents as rapidly progressive retinal degeneration, often accompanied by polyphagia, weight gain, polydipsia, polyuria, and hyposmia. Alström syndrome (AS) and Bardet-Biedl syndrome (BBS) are rare human autosomal recessive genetic disorders marked by progressive retinopathy, polyphagia, obesity, polydipsia, polyuria, and hyposmia, with varying degrees of phenotypic severity. While the etiology of AS and BBS is partially understood, the cause of acquired SARDS remains elusive. Historically, scientific inquiry has focused on an immunologic insult and/or endocrinopathy as the cause of SARDS. Clinicians have often pointed to these Cushingoid symptoms mentioned above in SARDS patients as evidence of a contributing endocrinopathy. However, systemic cortisol concentrations, both pre- and post-ACTH stimulation, typically do not differ appreciably between normal patients and those with SARDS. Blindness due to photoreceptor degeneration, along with the observed Cushingoid symptoms, may result from dysfunctional or absent primary cilia, as documented in human AS and BBS cases. Recognizing SARDS as a possible acquired ciliopathy may be the first step toward seeking effective treatments.
2025-06-16 | Should GLP-1 receptor agonist therapy be used to treat obesity in Bardet-Biedl syndrome?
Bardet-Biedl syndrome (BBS) is a complex genetic condition that can affect multiple organ systems, frequently causing pigmentary retinopathy, renal abnormalities, polydactyly, and obesity. Metabolic disturbances including obesity, unsuppressed appetite, and an increased risk of type 2 diabetes (T2D) present clinical management challenges. In this issue of the JCI, Singh et al. present a mouse model of a specific BBS subtype with genetic deletion of the Bbs5 gene. The model recapitulates many of the clinical features observed in patients living with BBS5 and sheds light on adipocyte biology, as well as the hypothalamic mechanisms driving hunger- and food-seeking behaviors that fuel the adverse metabolic phenotype. Importantly, exogenous GLP-1 receptor agonist treatment suppressed both appetite and weight, opening opportunities for direct translation into the clinical setting.
small molecules
2026-09-28 | Ciliary Membrane Lipid Homeostasis in Health and Disease
The ciliary membrane is an active, highly specialized lipid landscape that dictates ciliary identity and function. Distinct from the surrounding plasma membrane, it exhibits a tailored lipid architecture-enriched in specific phosphoinositides, cholesterol, and sphingolipids-that shapes membrane curvature and establishes spatial platforms for signaling cascades. Emerging evidence indicates that disrupting the lipid microenvironment gives rise to a distinct spectrum of ciliopathies, driven by mislocalized signaling receptors, impaired intraflagellar transport (IFT), and disintegrated inner structures. This review bridges biophysical membrane dynamics with genetic pathology, positioning ciliary lipids not merely as structural components, but as active orchestrators of ciliary gatekeeping, cilia motility, and cilia signal transduction. By remapping the molecular mechanics of lipid dysregulation in diseases such as Bardet-Biedl syndromes, we highlight how targeting the ciliary lipidome opens new therapeutic avenues for human ciliopathies.
2026-09-16 | BBS10 ‑related Bardet‑Biedl syndrome with an atypical presentation of diabetes mellitus: A case report
Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive ciliopathy characterized by extensive clinical heterogeneity, which often complicates its diagnosis.The present study reported the case of a 31-year-old woman who presented with longstanding, poorly controlled type 2 diabetes mellitus and its associated complications.The patient exhibited classic features including Class I obesity, retinal dystrophy, postaxial polydactyly, renal dysfunction and hypergonadotropic hypogonadism.A definitive diagnosis was established through whole-exome sequencing, which identified compound heterozygous pathogenic variants in the BBS10 gene (a nonsense mutation, p.Arg256 * and a missense mutation, p.Gly180Glu).This case is novel in presenting with adult-onset diabetes as the primary complaint, highlighting the necessity of including BBS in the differential diagnosis of patients with early-onset metabolic disorders and multisystem involvement.Of note, the patient's glycemic control improved after treatment with a glucagon-like peptide-1 receptor agonist (semaglutide).This observation provides important longitudinal evidence suggesting a promising therapeutic strategy for managing metabolic dysfunction in BBS, potentially by engaging residual G-protein-coupled receptor signaling pathways despite underlying ciliary defects.
2026-09-15 | Setmelanotide Response Variability in Two Genetically Confirmed Pediatric Kidney Transplant Recipients with Bardet-Biedl Syndrome.
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy associated with hyperphagic obesity and kidney disease. Evidence on setmelanotide after pediatric kidney transplantation is limited. We evaluated two children with BBS treated with setmelanotide after kidney transplantation, collecting anthropometric, hunger, metabolic, graft-function, cyclosporine and genetic data. Patient 1, a 17-year-old boy with a homozygous pathogenic SDCCAG8 exon deletion, improved over 12 months: weight 55.6 to 48.0 kg, BMI 26.6 to 23.0 kg/m2, BMI-for-age z-score +1.60 to +0.43, maximal-hunger score 8/10 to 5/10, and HbA1c 6.5% to 5.1%. Patient 2, an 8-year-old girl with a homozygous likely pathogenic BBS5 splice-site variant and a heterozygous PCSK1 N221D variant, showed reduced hunger and an initial z-score fall from +6.10 to +5.69 by month 2.5, meeting the 0.2-point threshold for clinically meaningful change; this was not sustained, and BMI rose from 38.0 to 42.7 kg/m2 by eight months despite a dose of 3 mg/day. Graft function and cyclosporine trough concentrations remained stable, and skin hyperpigmentation was the only treatment-related adverse effect. In these two patients, setmelanotide was not associated with graft deterioration or altered cyclosporine trough concentrations, although two cases cannot establish safety. The divergent trajectories highlight interindividual variability; the role of PCSK1 N221D remains uncertain, and these observations are hypothesis-generating.
2026-09-15 | Sequential liraglutide and setmelanotide therapy in Bardet-Biedl Syndrome: metabolic and renal outcomes in a real-world case report and literature review.
Bardet-Biedl syndrome (BBS) is a syndromic ciliopathy characterized by multiple clinical features, including obesity and kidney disease. Therapeutic options remain limited. Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is approved for obesity in BBS, but real-world data in adults is scarce. This case highlights the synergistic metabolic and nephroprotective effects of a sequential therapeutic strategy combining a glucagon-like peptide-1 (GLP-1) receptor agonist and a MC4R agonist. We report the case of a 37-year-old male with genetically confirmed BBS due to compound heterozygous likely pathogenic BBS10 variants presenting with obesity, insulin resistance, dyslipidemia, albuminuria and metabolic dysfunction-associated steatotic liver disease (MASLD). Treatment with liraglutide induced modest weight loss (-3.4%, BMI 35.2→34 kg/m²), improved urinary albumin-to-creatinine ratio (uACR) and liver enzymes levels within 8 months. Following discontinuation of liraglutide, setmelanotide therapy was subsequently initiated. After 12 months of treatment, the patient achieved a 10.5% weight loss compared with baseline (BMI 35.2→31.5 kg/m²), normalization of liver transaminases, reduced liver stiffness, and sustained improvement in uACR, while eGFR remained stable. Fasting insulin and HOMA-IR improved. Metformin, statin, and fenofibrate were discontinued, though fenofibrate was later reintroduced for hypertriglyceridemia. Two interventional studies (n≃10-40, 3-52 weeks) similarly reported consistent reduction in metabolic syndrome burden (METs-Z-BMI-score), liver steatosis, stiffness, and enzymes, while renal biomarkers showed stabilization or improvement, supporting potential hepatoprotective and reno-protective effects. Setmelanotide promoted clinically meaningful weight loss and improved liver, kidney, and metabolic parameters in an adult patient carrying BBS10-likely pathogenic variants. Together with emerging evidence for interventional studies, these findings suggest that MC4R agonism may confer organ-level and cardiometabolic benefits beyond weight reduction.
2026-09-11 | Supplemental Material for: Sequential liraglutide and setmelanotide therapy in Bardet-Biedl Syndrome: metabolic and renal outcomes in a real-world case report and literature review
IntroductionBardet–Biedl syndrome (BBS) is a syndromic ciliopathy characterized by multiple clinical features, including obesity and kidney disease.Therapeutic options remain limited. Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is approved for obesity in BBS, but real-world data in adults is scarce. This case highlights the synergistic metabolic and nephroprotective effects of a sequentialtherapeutic strategy combining a glucagon-like peptide-1 (GLP-1) receptor agonist and a MC4R agonist.Case PresentationWe report the case of a 37-year-old male with genetically confirmed BBS due to compound heterozygouslikelypathogenicBBS10 variants presenting with obesity, insulin resistance, dyslipidemia, albuminuria and metabolic dysfunction–associated steatotic liver disease (MASLD). Treatment with liraglutide induced modest weight loss (–3.4%, BMI 35.2→34 kg/m²), improved urinary albumin-to-creatinine ratio (uACR) and liver enzymes levels within 8 months.Following discontinuation of liraglutide, setmelanotide therapy wassubsequentlyinitiated. After 12 months of treatment, the patient achieved a 10.5% weight loss compared with baseline (BMI 35.2→31.5 kg/m²), normalization of liver transaminases, reduced liver stiffness, and sustained improvement in uACR, while eGFR remained stable. Fasting insulin and HOMA-IR improved. Metformin, statin, and fenofibrate were discontinued, though fenofibrate was later reintroduced for hypertriglyceridemia. Two interventional studies (n≃10–40, 3–52 weeks) similarly reported consistent reduction in metabolic syndrome burden (METs-Z-BMI-score), liver steatosis, stiffness, and enzymes, while renal biomarkers showed stabilization or improvement, supporting potential hepatoprotective and reno-protective effects. ConclusionSetmelanotide treatment was associated with clinically meaningful weight loss and improvements in liver, kidney, and metabolic parameters in this adult patient with BBS. This case supports the potential role of setmelanotide in the multidisciplinary management of BBS and highlights the need for further studies to better define its effects beyond weight reduction.
gene therapies
2026-08-14 | Clinical, Genetic, and Endocrine Features of Bardet-Biedl Syndrome in a Pediatric and Adult Cohort.
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder characterized by clinical and genetic heterogeneity. Data on the prevalence of clinical manifestations and comorbidities in BBS, particularly in pediatric patients, are limited. This study aimed to assess the prevalence and various manifestations of endocrine and other clinical comorbidities among pediatric and adult patients with BBS. This retrospective chart review included pediatric and adult patients with BBS evaluated at an academic tertiary care center in the United States between 2000 and 2024. The study included 31 patients (7 children and 24 adults) with seven identified pathogenic variants associated with BBS. The most common genetic etiology was biallelic variants in BBS1 (36%). Obesity was diagnosed in 86% of children and 100% of adults. No children had diabetes or prediabetes, whereas 46% of adults were affected. Dyslipidemia was identified in 29% of children and 46% of adults. No thyroid abnormalities were identified in children, whereas 25% of adults were affected. Retinal dystrophy was present in 71% of children and 96% of adults. Polydactyly was observed in 100% of children and 75% of adults. Chronic kidney disease was present in 29% of children and 63% of adults. This study highlights the clinical heterogeneity and substantial multisystem burden of BBS across pediatric and adult patients. The greater prevalence of diabetes/prediabetes, dyslipidemia, thyroid abnormalities, chronic kidney disease, and visual impairment among adults suggests that these complications may emerge or progress over time. Early recognition, proactive longitudinal surveillance, and comprehensive multidisciplinary care are essential to optimize management across the lifespan.
2026-01-19 | Retinal Degeneration and Visual Outcomes in Patients With Bardet-Biedl Syndrome: Genotypic Influences From a Caribbean Cohort.
Background The Bardet-Biedl syndrome (BBS) is a rare multisystem ciliopathy characterized by retinal degeneration, polydactyly, truncal obesity, hypogonadism, and hypogonadotropism. Progressive rod-cone dystrophy leads to early-onset vision loss. Despite increased genetic screening, BBS remains underdiagnosed in Caribbean populations. This study aims to describe the genetic and ocular phenotype of patients with BBS in Puerto Rico and explore genotype-phenotype correlations. Methods We conducted a retrospective chart review of 36 genetically confirmed BBS patients from a hereditary retinal disease clinic in Puerto Rico. Data collected included best-corrected visual acuity (BCVA), refractive error, visual field mean deviation (MD), and macular optical coherence tomography (OCT) measurements (volume and thickness). Genetic testing identified the BBS subtype and zygosity. Descriptive and statistical analyses were performed. The study was approved by a certified institutional review board (IRB). Results Age ranged from three to 69 years old. Mutations in the BBS1 gene were most frequent (86%), followed by BBS7 (8%), BBS10 (3%), and BBS19 (3%). Most patients had homozygous mutations in the BBS1 (%). The mean BCVA was 2.0 logMAR OD and 2.1 logMAR OS. Patients with homozygotic mutations in the BBS1 had worse vision than compound heterozygotes (p=0.025). Upon visual field examination, the MD was -27.6 dB OD and -28.3 dB OS. Near-absent visual fields occurred in patients with advanced disease. Macular volume and thickness averaged 8.2 mm³/227 µm (OD) and 7.7 mm³/216 µm (OS). Structural damage was associated with inner/outer segment disruption on OCT. Conclusions Mutations in the BBS1 are the most frequent in Puerto Rico, often associated with profound visual impairment and retinal thinning. These findings underscore the importance of early ophthalmic evaluation and genetic testing in patients with syndromic retinitis pigmentosa. Genotype-specific differences in visual decline support personalized surveillance and future therapeutic planning.
2025-11-02 | Bardet-Biedl Syndrome: Ocular Genetic Trials
Bardet-Biedl Syndrome is a rare genetic disorder with autosomal recessive inheritance that affects multiple organ systems. It is characterized by retinal dystrophy, obesity, polydactyly, renal anomalies, and cognitive impairment, this syndrome prominently involves ocular manifestations, which constitute one of the major sources of morbidity. In the majority of cases, progressive retinal degeneration begins in childhood or early adulthood, leading to significant vision loss. The molecular pathogenesis of BBS is associated with genetic mutations that disrupt the function of primary cilia. These mutations occur in genes encoding structural or regulatory components of the BBSome complex, which plays a crucial role in fundamental cellular processes such as cytoskeletal organization, protein trafficking, and intracellular signaling. In recent years, ocular genetic studies have expanded the spectrum of known mutations through functional analyses, while animal models have provided deeper insights into the molecular mechanisms underlying retinal pathology. From a therapeutic standpoint, gene replacement strategies have shown promising results at the preclinical level; however, the considerable genetic heterogeneity and the multisystemic nature of the syndrome pose challenges for the clinical translation of these approaches.
2025-10-29 | Clinical spectrum of Bardet-Biedl Syndrome: A case series
Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by a wide spectrum of clinical manifestations, including retinal dystrophy, obesity, post-axial polydactyly, learning disabilities, hypogonadism, and renal abnormalities. Early recognition is often challenging due to its gradual progression and overlapping features with other conditions, particularly in resource-limited settings where genetic testing is not readily available. We report a series of four Bangladeshi cases with variable phenotypic expressions of BBS. All patients presented with progressive visual impairment, obesity, and polydactyly, accompanied by additional features such as diabetes mellitus, dyslipidemia, hypogonadism, renal impairment, developmental delay, and behavioral disturbances. Diagnosis was established based on Beales’ clinical criteria, with patients meeting multiple primary and secondary features. Renal involvement was observed in two cases, including diabetic nephropathy and focal segmental glomerulosclerosis, underscoring its role as a major determinant of morbidity and mortality. Management required a multidisciplinary approach involving endocrinology, ophthalmology, nephrology, and mental health services, alongside lifestyle modification, pharmacotherapy, and family counseling. This case series highlights the clinical heterogeneity of BBS, the importance of heightened clinical suspicion for early detection, and the need for comprehensive multidisciplinary care to improve long-term outcomes in affected individuals. [J Assoc Clin Endocrinol Diabetol Bangladesh, 2025;4(Suppl 1): S49]
2025-09-02 | Atypical Retinitis Pigmentosa with Systemic Features in Bardet--Biedl Syndrome
Title:Atypical Retinitis Pigmentosa with Systemic Features in Bardet–Biedl SyndromeAuthor1-Muhammad Umar Ahsan, MBBS E-mail:umarahsan219@gmail.com Affiliation: D.G.Khan medical college, Dera Ghazi Khan, Pakistan ORCID: 0009-0008-0627-2521 2- Dr Saba S
cell therapies
2025-10-22 | Renal Transplant in a Bardet-Biedl Syndrome Patient: A First Case From Azerbaijan.
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by multisystem involvement, with renal pathology, including end-stage renal disease, being a major cause of morbidity and mortality. This case report presents a 14-year-old boy with BBS and end-stage renal disease who underwent a successful living donor kidney transplantation, marking the first reported case in Azerbaijan. Despite multiple comorbidities, including obesity, hypertension, and high panel reactive antibody levels, the patient achieved stable graft function with a rapid postoperative creatinine decline. Postoperative management focused on immunosuppression and lifestyle adjustments. This case contributes to the limited literature on BBS, highlighting both the challenges and favorable outcomes of renal transplantation in patients with this rare genetic disorder.
2013-04-01 | Proteomic Analysis of Human Blastocoel Fluid and Blastocyst Cells
Human embryonic stem cells (hESCs) are derived from the inner cell mass (ICM) of the blastocyst and can differentiate into any cell type in the human body. These cells hold a great potential for regenerative medicine, but to obtain enough cells needed for medical treatment, culture is required on a large scale. In the undifferentiated state, hESCs appear to possess an unlimited potential for proliferation, but optimal, defined, and safe culture conditions remain a challenge. The aim of the present study was to identify proteins in the natural environment of undifferentiated hESCs, namely, the blastocoel fluid, which is in contact with all the cells in the blastocyst, including hESCs. Fifty-three surplus human blastocysts were donated after informed consent, and blastocoel fluid was isolated by micromanipulation. Using highly sensitive nano-high-pressure liquid chromatography–tandem mass spectrometry, 286 proteins were identified in the blastocoel fluid and 1,307 proteins in the corresponding cells of the blastocyst. Forty-two were previously uncharacterized proteins—8 of these originated from the blastocoel fluid. Furthermore, several heat shock proteins (Hsp27, Hsp60, Hsc70, and Hsp90) were identified in blastocoel fluid together with zona pellucida proteins (ZP2–4), Vitamin D-binding protein, and Retinol-binding protein 4. Proteins that regulate ciliary assembly and function were also identified, including Bardet-Biedl syndrome protein 7. This study has identified numerous proteins that cells from the ICM of the human blastocyst are exposed to via the blastocoel fluid. These results can be an inspiration for the development of improved culture conditions for hESCs.
other
2025-11-24 | Splice-switching antisense oligonucleotides correct cryptic exon inclusion and restore SDCCAG8 protein in Bardet-Biedl Syndrome.
Bardet-Biedl Syndrome (BBS) is a ciliopathy often associated with progressive blindness and obesity. A patient presenting with BBS was discovered to have two mutations within 55bp of each other in intron 7 of SDCCAG8 (BBS16). One of the biallelic mutations, c.740+356C>T, causes inclusion of cryptic exon(s) containing premature termination codons, while c.740+301G>A has not been characterized. We hypothesized that antisense oligonucleotides (ASOs) complementary to the patient's mutations or to the cryptic exon splice sites would correct the splicing of SDCCAG8 between exons 7 and 8 to prevent cryptic exon inclusion and restore SDCCAG8 expression. We systematically screened 20nt-long ASOs tiled across each mutation and ASOs targeting the 3' splice sites of the cryptic exons in patient-derived fibroblasts, using RT-PCR assays to assess exon 7 and 8 splicing. We identified one ASO for each mutation and a cryptic exon-targeting ASO that restored the splicing pattern to that observed in an unaffected cell line. Lead ASOs were further investigated through RT-PCR, RNA sequencing, and western blotting to confirm ASO-mediated restoration of wild-type transcript and protein. Notably, ASO 20, which targets the cryptic exon 7a/7a' splice site rather than patient-specific mutations, achieved the greatest rescue effect, increasing exon 7-8 splicing from 0% to an average of 26% and restoring SDCCAG8 protein from undetectable levels to approximately 40% of wild-type expression. This mutation-agnostic approach could benefit multiple patients with cryptic exon inclusion in this region of SDCCAG8, expanding therapeutic impact beyond traditional N-of-1 ASO strategies. These findings establish a molecular foundation for clinical development of ASO therapy for BBS caused by SDCCAG8 splicing defects.
2025-07-28 | Analysis of the Body Mass Index of Latino Patients With Bardet-Biedl Syndrome.
Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive disorder characterized by multi-systemic manifestations, including truncal obesity, rod-cone dystrophy, polydactyly, and learning disabilities. The syndrome is associated with mutations in at least 28 genes, with BBS1 being the most common. This study investigates the correlation between body mass index (BMI) and specific genetic mutations in a cohort of 27 Latino patients with BBS. A chart review of 27 patients with BBS was conducted. Comprehensive ophthalmic evaluations, including best corrected visual acuity (BCVA), optical coherence tomography, and electroretinography, were performed. Genetic screening was conducted using next-generation sequencing with a focus on BBS1, BBS7, and BBS19 mutations. BMI was classified into normal, overweight, and obese categories. Statistical analyses (chi-square and Kruskal-Wallis test) were used to evaluate the data. The cohort had a mean age of 39 years, with 21 patients (77.8%) carrying mutations in the BBS1 gene. Among the cohort, a total of 14 patients (51.9%) were classified as obese, 10 (37.0%) as overweight, and three (11.1%) as normal weight. Obesity was most common in patients with BBS1 mutations, with 11 obese patients (78.6%) carrying BBS1 mutations, while patients with BBS7 and BBS19 mutations exhibited lower rates of obesity. Among obese patients, 10 (71.4%) were homozygous for mutations in the associated genes, and three (21.4%) were compound heterozygotes. Gender did not show statistically significant differences in obesity prevalence; however, male patients were more frequently overweight. This study confirms a strong association between BBS1 mutations and obesity in BBS patients, with homozygous and compound heterozygous mutations contributing to more severe clinical manifestations. Further research is required to better understand the genotype-phenotype relationship and to explore the role of environmental factors, such as physical activity, in modifying obesity outcomes. Larger, more diverse studies are needed to validate these findings and to develop targeted therapeutic strategies for BBS-related obesity.
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Drug Discovery Landscape
5 orphan drug designations for Bardet-Biedl syndrome, including 2 approved therapies.
5 orphan drug designations for Bardet-Biedl syndrome, including 2 approved therapies.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
recombinant, replication incompetent adeno-associated virus viral vector platform with a serotype 8 capsid and a cDNA encoding the human BBS10 gene (AAV8-RK-BBS10) | gene therapies | FDA | — | MeiraGTx UK II Ltd |
adeno-associated virus 2/8 expressing human BBS1 gene | gene therapies | FDA | Axovia Therapeutics | |
adeno-associated virus 2/9 expressing human BBS1 gene | gene therapies | FDA | Axovia Therapeutics | |
setmelanotide [Imcivree] | small molecules | FDA | Approved | Rhythm Pharmaceuticals, Inc |
Setmelanotide [Imcivree] | small molecules | EMA | Approved | Rhythm Pharmaceuticals Netherlands B.V. |
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