First case report of Cohen syndrome in the Tunisian population caused by VPS13B mutations

Abstract

Background: Cohen syndrome is a rare autosomal recessive developmental disorder that comprises variable clinical features counting developmental delay, pigmentary retinopathy, myopia, acquired microcephaly, truncal obesity, joint hypermobility, friendly disposition and intermittent neutropenia. VPS13B (vacuolar protein sorting 13, yeast, homologue of B) gene is the only gene responsible for Cohen Syndrome, causative mutations include nonsense, missense, indel and splice-site variants. The integrity of the Golgi apparatus requires the presence of the peripheral membrane protein VPS13B that have an essential function in intracellular protein transport and vesicle-mediated sorting.

Case presentation: In this study, we performed whole exome sequencing (WES) in a Tunisian family with two young cases having developmental delay, hypotonia, autism spectrum disorder, ptosis and thick hair and eyebrows. The proposita presented also pigmentory retinopathy. Compound heterozygous mutation in VPS13B gene was detected by WES. This mutation inherited from healthy heterozygous parents, supports an unpredictable clinical diagnosis of Cohen Syndrome. The proband's phenotype is explained by the presence of compound heterozygous mutations in the VPS13B gene. This finding refined the understanding of genotype-phenotype correlation.

Conclusions: This is the first report of a Tunisian family with Cohen syndrome mutated in the VPS13B gene.

Keywords: Cohen syndrome; Compound heterozygous mutation; VPS13B gene.

Fig. 1

a The proband. b the brother of the proband. c Proband’s MRI (1) sections showing dysmorphic and thick corpus callosum and (2, 3) the lateral ventricular asymmetry

Fig. 2

a Integrative Genomics Viewer of short read alignment indicated the compound heterozygous variant identified by exome sequencing (100,479,778 T/−,100712001AT/−) in the VPS13B gene. b Sanger validation shows the compound heterozygosity of the proband II1 formed by the c.3582delT mutation, and the c.6295_6296delAT mutation

Fig. 3

a Pedigree of the Tunisian family and compound heterozygosity of the proband, formed by the c.3582delT mutation, inherited from the father of the proband and also present in her brother, and the c.6295_6296delAT mutation inherited from the mother. The 2 mutations are shown in black, and in white the wild type alleles (WT). b Sanger validation shows segregation of the VPS13B mutations in the four family members