title: C2orf37 mutational spectrum in Woodhouse-Sakati syndrome patients.
abstract: Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive disorder that encompasses hypogonadism, deafness, alopecia, mental retardation, diabetes mellitus and progressive extrapyramidal defects. The syndrome is caused by mutation of the C2orf37 gene. Here we studied a cohort of seven new cases from three ethnic backgrounds, presenting with the hallmarks of WSS, in an effort to extend the mutational spectrum of this disorder. Genetic analysis revealed a novel mutation in each of the four families investigated, of which three were nonsense mutations and the fourth was a splice site ablation. We also examined a separate collection of 11 cases presenting with deafness and dystonia, two constituents of WSS, but found no pathogenic changes. This study doubles the number of known mutations for this disorder, confirms that truncating mutations in C2orf37 are the only known cause of WSS, and suggests that mutations in this gene do not contribute significantly to cases presenting with isolated elements of WSS such as deafness and dystonia. The lack of correlation between clinically expressivity of WSS and the site of the eight truncating mutations strongly supports that they are equally null, while the intrafamilial variability argues for an important role of modifiers in this disease.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
authors.forename: A M
authors.initials: AM
authors.lastname: Alazami
authors.forename: S A
authors.initials: SA
authors.lastname: Schneider
authors.forename: D
authors.initials: D
authors.lastname: Bonneau
authors.forename: L
authors.initials: L
authors.lastname: Pasquier
authors.forename: M
authors.initials: M
authors.lastname: Carecchio
authors.forename: M
authors.initials: M
authors.lastname: Kojovic
authors.forename: K
authors.initials: K
authors.lastname: Steindl
authors.forename: M
authors.initials: M
authors.lastname: de Kerdanet
authors.forename: M M
authors.initials: MM
authors.lastname: Nezarati
authors.forename: K P
authors.initials: KP
authors.lastname: Bhatia
authors.forename: B
authors.initials: B
authors.lastname: Degos
authors.forename: E
authors.initials: E
authors.lastname: Goh
authors.forename: F S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D000293:Adolescent; D000328:Adult; D000505:Alopecia / Q000235:genetics; D001145:Arrhythmias, Cardiac / Q000235:genetics; D001480:Basal Ganglia Diseases; D001483:Base Sequence; D002648:Child; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000235:genetics; D006801:Humans; D007006:Hypogonadism / Q000235:genetics; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D043743:Ubiquitin-Protein Ligase Complexes
chemical_list: C556016:DCAF17 protein, human; D009687:Nuclear Proteins; D043743:Ubiquitin-Protein Ligase Complexes