2026-06-30 | Compensatory clonal hematopoiesis in patients with Shwachman–Diamond syndrome
Introduction. Shwachman–Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome characterized by a high risk of developing myeloid malignancies. Aim: to determine the spectrum of compensatory genetic events in SDS as well as to analyze their potential role in the clinical course of the disease. Materials and methods. The study included 41 patients with confirmed SDS. For the analysis of somatic alterations, we employed high-throughput sequencing of the “Clonality of Hematopoiesis” targeted gene panel as well as cytogenetic methods. Results. Compensatory somatic events were detected in 31.7% of the patients. The most frequent alterations were genetic variants in the EIF6 gene, as well as the i(7q) and del(20q) clonal cytogenetic abnormalities. Generally, these changes were not accompanied by clinical or morphological signs of myeloid transformation. Conclusion. The obtained data suggest a possible role of somatic genetic compensation in maintaining the viability of hematopoietic cells in SDS. Therefore, the detection of markers of clonal expansion necessitates dynamic molecular monitoring.
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2026-06-28 | Generation of iPSC and isogenic gene-corrected lines from a patient with Shwachman Diamond syndrome.
Shwachman Diamond Syndrome (SDS) is an inherited bone marrow failure and leukemia predisposition syndrome characterized by exocrine pancreatic insufficiency, skeletal dysplasia and bone marrow failure. SDS is inherited in an autosomal recessive manner and most patients with SDS carry biallelic mutations in the SBDS gene. We generated an iPSC line from a patient biallelic SBDS mutations (c.258 + 2 T > C & c.183-184delinsCT(p.Lys62*) along with a corresponding isogenic control line correcting the splice site mutation with a cytosine base editor.
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2026-06-12 | A Case Report of Shwachman-Diamond Syndrome Caused by Heterozygous Variants in the EFL1 Gene and Literature Review.
This investigation reports on a Shwachman-Diamond syndrome (SDS) case arising from compound heterozygous genetic variations affecting the EFL1 locus. A systematic review of published literature was undertaken to compile data on clinical manifestations, management strategies, and prognostic indicators in SDS cases with identified EFL1 genetic alterations. The clinical data of a neonatal SDS patient, whole exome sequencing (WES) results, and the pathogenicity of the variants were analyzed. A comprehensive survey of applicable medical literature published up to March 2025 was executed to identify and synthesize the clinical phenotypes associated with this condition. WES identified compound heterozygous variants within the patient's EFL1 gene: c.2935C>T (p.R979C) and c.3149_3151delCAC (p.P1050del). Bioinformatics analysis indicated these variations were damaging. Seven articles reported a total of 20 cases of this disease, with predominant phenotypes including exocrine pancreatic insufficiency, hematologic abnormalities, and metaphyseal dysplasia. Among the 20 previously reported cases, 16 distinct EFL1 variants were identified, and the current case adds 2 novel variants. SDS caused by EFL1 gene defects primarily presents as bone marrow failure, with treatment mainly focused on symptomatic management. We report a neonatal SDS patient with the earliest onset of symptoms. The c.2935C>T and c.3149_3151delCAC compound heterozygous variants reported in this study expand the mutational spectrum of this disease.
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