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

Eur J Hum Genet. 2009 Aug;17(8):1076-9. doi: 10.1038/ejhg.2008.273. Epub 2009 Feb 4.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Case-Control Studies
  • DNA Mutational Analysis
  • Hearing Loss, Sensorineural / complications
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Male
  • Mutation, Missense
  • Pedigree
  • Scalp / abnormalities*
  • Siblings*
  • Syndrome
  • Vesicular Transport Proteins / genetics*

Substances

  • VPS13B protein, human
  • Vesicular Transport Proteins