Cohen syndrome due to a novel stop-gain mutation in VPS13B gene: A case report and comparative study in affected siblings worldwide

Abstract

Abstract Background Cohen syndrome (CS) is a highly rare heterogeneous disorder associated with mutations in the vacuolar protein sorting 13 homolog B (VPS13B) gene. CS is mainly characterized by intellectual disability, microcephaly, progressive retinopathy, hypotonia, obesity, neutropenia and dysmorphic facial features. Case presentation : Here, we report two affected siblings suspicious to CS. Our objectives were the delineation of gene mutation causing this rare condition and comparison of observed manifestations with symptoms reported in other CS affected siblings worldwide. Whole exome sequencing (WES) in combination with Sanger sequencing were utilized to identify the disease-causing mutation in the affected siblings. Subsequently, to elucidate the effects of the mutation found, clinical data of patients were collected. Moreover, the possible impact of the identified mutation on the corresponding protein was analyzed using bioinformatics tools. A novel homozygous stop-gain mutation NM_015243: c.1043G > A: p.W348X in the VPS13B gene was identified in the proband. This mutation was confirmed by Sanger sequencing in the affected siblings and segregated with the autosomal recessive (AR) inheritance pattern of CS. Moreover, in-silico approaches highly confirmed the disease-causing nature of the identified mutation. Conclusion Our findings could expand the mutations spectrum of CS and the comparative study of all reported manifestations in CS affected siblings throughout the world, clearly shed light the common and uncommon manifestations of CS in different affected siblings with different VPS13B gene mutations. These results could be also useful in genetic diagnosis and counseling in CS affected patients.