A novel VPS13B mutation in two brothers with Cohen syndrome, cutis verticis gyrata and sensorineural deafness

Abstract

We have earlier described a syndrome characterized by microcephaly, cutis verticis gyrata, retinitis pigmentosa, cataracts, hearing loss and mental retardation (Mendelian inheritance in man (MIM) no: 605685) in two brothers from a non-consanguineous Lebanese family. In view of the rarity of the disorder and the high rate of inbreeding in the Lebanese population, we assumed an autosomal recessive trait inherited from a common ancestor. A genomewide scan was performed. The single locus on the long arm of chromosome 8 that showed homozygosity by descent comprised the gene responsible for Cohen syndrome (CS), VPS13B. We then sequenced VPS13B in the patients and found a homozygous splice site mutation. Several possible explanations for the overlap between CS and the clinical features observed in our patients are discussed. Our data highlight the potential of high-resolution homozygosity mapping in small populations with a high rate of inbreeding.

Value of whole exome sequencing for syndromic retinal dystrophy diagnosis in young patients

“…By 7 and 4 years of age, our patients had moderate to severe intellectual impairment, microcephaly, myopia, pigmentary retinal degeneration as noted in other Lebanese patients with this condition (Table 1). 4,15,16 Two brothers with CS of Lebanese ancestry had cutis verticis gyrata of the scalp, 16,17 but this was not present in our patients and has not been described in other CS patients. These two brothers with CS of Lebanese ancestry also had sensorineural hearing loss with onset in the mid-to late 20s, a feature not usually described in CS, although this may require examination of older age patients for recognition.…”

Is cutis verticis Gyrata‐Intellectual Disability syndrome an underdiagnosed condition? A case report and review of 62 cases

“…Moreover, the presence additional microcephaly in these brothers, which was not mentioned in the family of Akesson may suggests further genetic heterogeneity, In this regard, we note that two brothers were reported with ID, microcephaly, CVG, retinitis pigmentosa, cataracts, and sensorineural deafness [Mégarbané et al, ]. The two brothers were later found to carry homozygous mutations in the Cohen gene VPS13B [Mégarbané et al, ]. CVG could be either part of the syndrome or be caused by mutations in a different gene.…”

Cutis verticis gyrata: Two cases associated with drug‐resistant epilepsy

“…() CVG‐ID was mainly identified in subjects living in psychiatric institutions, where it was a prevalence of up to 11.4% 11 . CVG was described in some genetic disorders 12‐14 ; however, the etiology and pathogenesis of CVG‐ID is unknown. According to Tucci et al, 3 () the clinical manifestations of CVG‐ID include cutis verticis gyrata that is evident after puberty, severe psychomotor retardation, childhood‐onset epilepsy, strabismus, and microcephaly.…”