title: A de novo missense mutation in a critical domain of the X-linked DDP gene causes the typical deafness-dystonia-optic atrophy syndrome.
abstract: We report the first de novo mutation in the DDP gene in a Dutch 11-year-old boy with deafness and dystonia. Previously reported mutations in the DDP gene have all been frameshifts/nonsense mutations or deletion of the entire gene as part of a larger deletion encompassing the BTK gene. The clinical presentation was uniformly characterised by sensorineural hearing loss, dystonia, mental deterioration, paranoid psychotic features, and optic atrophy, indicating progressive neurodegeneration. Our report illustrates that de novo mutations occur and that a missense mutation, C66W, may cause an equally severe clinical picture. The diagnosis of sensorineural hearing impairment associated with neurologic and visual disability in a male, therefore, should encourage the search for mutations in the DDP gene, even in sporadic cases. The association of deafness-dystonia syndrome with a missense mutation provides valuable information for in vitro investigations of the functional properties of the deafness-dystonia peptide which was recently shown to be the human homolog of a yeast protein, Tim8p, belonging to a family of small Tim proteins involved in intermembrane protein transport in mitochondria.
authors.affiliation: Department of Medical Genetics, University Hospital of Tromsø, Norway. lisbetht@fagmed.uit.no
authors.forename: L
authors.initials: L
authors.lastname: Tranebjaerg
authors.forename: B C
authors.initials: BC
authors.lastname: Hamel
authors.forename: F J
authors.initials: FJ
authors.lastname: Gabreels
authors.forename: W O
authors.initials: WO
authors.lastname: Renier
authors.forename: M
authors.initials: M
authors.lastname: Van Ghelue
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D004421:Dystonia / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009896:Optic Atrophy / Q000235:genetics*; D010375:Pedigree; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics*; D013577:Syndrome; D014960:X Chromosome
chemical_list: D011506:Proteins