title: 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.
authors.affiliation: Université Saint-Joseph, Beirut, Lebanon.
authors.forename: André
authors.initials: A
authors.lastname: Mégarbané
authors.forename: Rima
authors.initials: R
authors.lastname: Slim
authors.forename: Gudrun
authors.initials: G
authors.lastname: Nürnberg
authors.forename: Inga
authors.initials: I
authors.lastname: Ebermann
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Hanno Jörn
authors.initials: HJ
authors.lastname: Bolz
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D012535:Scalp / Q000002:abnormalities*; D035781:Siblings; D013577:Syndrome; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C475722:VPS13B protein, human; D033921:Vesicular Transport Proteins