Ophthalmic features of retinitis pigmentosa in Cohen syndrome caused by pathogenic variants in the VPS13B gene

Purpose The aim of this study is to report on the phenotype and genotype of five patients diagnosed with Cohen syndrome, an extremely rare autosomal recessive disorder manifesting with mental and physiological defects. Methods Five patients from three German families and one Syrian family underwent a comprehensive ophthalmological examination. The scheduled visual acuity measurements, fundus ophthalmoscopy, spectral domain optical coherence tomography (OCT), full‐field electrophysiological recordings of scotopic and photopic electroretinograms (ERGs) and colour vision testing could not be carried out in all subjects, because of the mental and physical retardation. The genetic diagnosis was achieved by next‐generation sequencing. Results The ophthalmic and systemic phenotype of the patients is typical for Cohen syndrome including myopia, night blindness, photophobia, fundus pigmentary changes and bull's eye maculopathy. Electroretinograms (ERGs) were extinguished in the four patients, whose recording was possible. Genetic testing revealed homozygous or two heterozygous bi‐allelic mutations in the VPS13B (COH1) gene in all five patients, with five different allelic variants observed. The homozygous mutation c.6055_6056delGA; p.Asp2019Glnfs*15 in two sibling patients as well as the homozygous nonsense mutation c.8112C>G;p.Tyr2704* have not previously been reported. Conclusions The phenotype of the five patients reported here is typical for Cohen syndrome; however, their genotype is heterogeneous. Two new allelic variants were found to be the causative mutation.