Deletions in the VPS13B (COH1) gene as a cause of Cohen syndrome.

[cohen syndrome]

Cohen syndrome is an autosomal recessive disorder that is characterized by mental retardation , facial dysmorphism , microcephaly , retinal dystrophy , truncal obesity , joint laxity and intermittent neutropenia . Mutations in the VPS 13 B (COH 1 ) gene underlie Cohen syndrome . In approximately 70 % of the patients mutations in the gene are identified on both alleles , while in about 30 % only a mutation in a single allele or no mutant allele is detected . The VPS 13 B locus was recently added to the growing list of benign copy number variants . We hypothesized that patients with unexplained Cohen syndrome would harbour deletions affecting the VPS 13 B locus . We screened 35 patients from 26 families with targeted array CGH and identified 7 copy number alterations : 2 homozygous and 5 heterozygous deletions . Our results show that deletions are an important cause of Cohen syndrome and screening for copy number alterations of VPS 13 B should be an integral part of the diagnostic work-up of these patients . These findings have important consequences for the diagnosis of patients with genetic disorders in general since , as we highlight , rare benign copy number variants can underly autosomal recessive disorders and lead to disease in homozygous state or in compound heterozygosity with another mutation .