2026-06-15 | Secukinumab for lamellar ichthyosis in an adolescent: a case report.
Lamellar ichthyosis (LI) is a rare hereditary disorder of keratinization, most commonly inherited in an autosomal recessive manner and frequently associated with pathogenic variants in the TGM1 gene. Patients usually present with generalized scaling, xerosis, and pruritus from birth. Current therapeutic options remain limited, and systemic retinoids are often associated with considerable adverse effects. A 14-year-old female individual presented with generalized pruritic, lamellar scale-like skin changes present since birth. The diagnosis of LI was established based on clinical findings, histopathological evaluation, and genetic testing [two pathogenic variants in the TGM1 gene, consistent with autosomal recessive congenital ichthyosis type 1, Online Mendelian Inheritance in Man (OMIM): 242300]. Oral administration of acitretin (10 mg twice daily) was initiated; however, treatment was discontinued due to elevated hepatic transaminase levels and severe xerosis with pruritus. Subcutaneous administration of secukinumab (150 mg weekly) was subsequently initiated. After five weekly doses, the dosing frequency was reduced to once monthly. Over 8 weeks, substantial clinical improvement was observed, with a satisfactory therapeutic response. The patient remained on active treatment at the time of reporting. Secukinumab appeared to be effective in this patient with LI and may warrant further investigation as a potential therapeutic option for inherited ichthyosis.
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2026-06-15 | Potential of 3D Skin Models and N/TERT-2G Cell Line in Genetic Research on Autosomal Recessive Nonsyndromic Epidermal Differentiation Disorders.
Autosomal recessive nonsyndromic epidermal differentiation disorders (AR-nEDDs), also known as autosomal recessive congenital ichthyosis (ARCI), are rare genetic skin diseases that lack curative treatments and can only be managed symptomatically. Their study is hampered by the limited availability of biological samples and donor tissues. Artificial skin models offer a valuable alternative for experimental research. Here, we generated epidermal skin equivalents (ESE) using primary keratinocytes from patients with AR-nEDDs carrying pathogenic variants in ALOX12B, CYP4F22, and CERS3, as well as immortalized N/TERT-2G cells. Whereas primary cells undergo senescence, N/TERT-2G cells offer a promising alternative to overcome this limitation. Histological staining and qPCR were applied to assess key epidermal proteins and AR-nEDD-related gene expression in patient- and control-derived models. Patient-derived ESE reproduced the major histopathological features and protein expression patterns characteristic of AR-nEDDs. In contrast, N/TERT-2G-based models showed earlier expression of 12R-LOX, CYP4F22, and CERS3 proteins in epidermal layers compared to healthy donor equivalents. These findings suggest that N/TERT-2G cells represent a reproducible platform for future gene-editing approaches of modelling epidermal differentiation disorders. However, as they do not inherently carry pathogenic variants, they are particularly suitable for gene-editing approaches such as CRISPR/Cas9-mediated disease modelling. Conversely, patient-derived keratinocyte models remain indispensable for validating disease mechanisms and evaluating therapeutic strategies.
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2026-06-09 | Role of hydrogel-based systems in the management of lamellar ichthyosis: A comprehensive review
A rare autosomal recessive congenital skin condition called lamellar ichthyosis is typified by aberrant keratinization and compromised epidermal barrier function. Mutations in genes including TGM1, ABCA12, ALOX12B, ALOXE3, and NIPAL4, which are essential for protein cross-linking and lipid metabolism in the stratum corneum, are the main cause of the disorder. Clinically, affected people frequently have a collodion membrane at birth that eventually sheds, exposing the body's massive, black, plate-like scales. Ectropion, eclabium, hypohidrosis, and heightened vulnerability to infections as a result of weakened skin integrity are other characteristics. According to epidemiology, lamellar ichthyosis is an uncommon condition that affects both sexes equally and has a global prevalence of between 1 in 100,000 and 300,000 people. Genetic testing may be used to assist the diagnosis, which is mostly clinical. In extreme cases, emollients, humectants, keratolytic agents, and systemic retinoids are used to relieve symptoms. The potential use of hydrogels as a successful therapeutic strategy for treating this illness has been brought to light by recent developments. Because of their high water content and biocompatibility, hydrogels improve medication penetration into the stratum corneum, decrease scaling, and offer constant hydration. Treatment results are further enhanced by their capacity to provide sustained and regulated drug release. All things considered, lamellar ichthyosis necessitates lifelong care, and new treatments like hydrogel-based formulations offer encouraging opportunities to enhance patient care and quality of life.
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2026-04-11 | Mutation Analysis in Ten Cases With PNPLA1-Nonsyndromic Epidermal Differentiation Disorder: Evidence of a Founder Effect.
Autosomal recessive congenital ichthyosis (ARCI) belongs to a heterogeneous group of nonsyndromic epidermal differentiation disorders (nEDD). Variants in PNPLA1, which encodes a transacylase essential for the formation of epidermal lipid barrier, underlie ARCI10. This study aims to unveil the underlying genetic basis in ten Chinese cases diagnosed with ARCI, and to determine the origin of a prevalent variant. Ten cases, encompassing twelve patients with ARCI, were recruited for this study. Whole-exome sequencing combined with Sanger sequencing was used to detect the underlying variants. Haplotype analysis using flanking highly polymorphic SNPs was used to trace the origin of the c.1300delG variant in the PNPLA1 gene. All patients developed generalized fine scales and erythema shortly after birth. Marked phenotypic heterogeneity was observed among the affected individuals, leading to diagnosis of either generalized or localized nEDD. In total, we detected three recurrent variants (c.1300delG, p.A434Hfs*22; c.434 T > C, p.Ile145Thr; c.488C > T, p.Pro163Leu) and five novel variants (c.205 + 1G > A, splicing; c.74C > T, p.Ser25Phe; c.473G > A, p.Cys158Tyr; c.731A > G, p.Tyr244Cys; c.1318C > T, p.Arg440*) in PNPLA1. The c.1300delG variant, prevalent in 7 unrelated ARCI cases, was associated with a common haplotype. Furthermore, we presented the beneficial effect of secukinumab treatment in one of our patients. Our findings suggest that the c.1300delG variant is a highly prevalent variant in Chinese PNPLA1-associated nEDD patients, and indicate that the recurrent variant may originate from a common ancestor in southern China, suggesting a regional founder effect. The observed response with secukinumab in one patient suggests that it might represent a potential therapeutic option for PNPLA1-nEDD patients.
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2026-02-07 | Editing the skin in place: In vivo genome correction of rare skin disease.
In this issue, Apaydin and Sadhnani et al. report in situ genome editing of human skin to correct a common disease-causing mutation underlying autosomal recessive congenital ichthyosis (ARCI).1 They combine a base editor, transient barrier modulation, and topical mRNA-lipid nanoparticle administration to restore clinically meaningful levels of transglutaminase 1 activity.
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