title: A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness.
abstract: In 1960, progressive sensorineural deafness (McKusick 304,700, DFN-1) was shown to be X-linked based on a description of a large Norwegian pedigree. More recently, it was shown that this original DFN-1 family represented a new type of recessive neurodegenerative syndrome characterized by postlingual progressive sensorineural deafness as the first presenting symptom in early childhood, followed by progressive dystonia, spasticity, dysphagia, mental deterioration, paranoia and cortical blindness. This new disorder, termed Mohr-Tranebjaerg syndrome (referred to here as DFN-1/MTS) was mapped to the Xq21.3-Xq22 region2. Using positional information from a patient with a 21-kb deletion in chromosome Xq22 and sensorineural deafness along with dystonia, we characterized a novel transcript lying within the deletion as a candidate for this complex syndrome. We now report small deletions in this candidate gene in the original DFN-1/MTS family, and in a family with deafness, dystonia and mental deficiency but not blindness. This gene, named DDP (deafness/ dystonia peptide), shows high levels of expression in fetal and adult brain. The DDP protein demonstrates striking similarity to a predicted Schizosaccharomyces pombe protein of no known function. Thus, is it likely that the DDP gene encodes an evolutionarily conserved novel polypeptide necessary for normal human neurological development.
authors.affiliation: Division of Medical and St. Thomas's London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Jin
authors.forename: M
authors.initials: M
authors.lastname: May
authors.forename: L
authors.initials: L
authors.lastname: Tranebjaerg
authors.forename: E
authors.initials: E
authors.lastname: Kendall
authors.forename: G
authors.initials: G
authors.lastname: Fontán
authors.forename: J
authors.initials: J
authors.lastname: Jackson
authors.forename: S H
authors.initials: SH
authors.lastname: Subramony
authors.forename: F
authors.initials: F
authors.lastname: Arena
authors.forename: H
authors.initials: H
authors.lastname: Lubs
authors.forename: S
authors.initials: S
authors.lastname: Smith
authors.forename: R
authors.initials: R
authors.lastname: Stevenson
authors.forename: C
authors.initials: C
authors.lastname: Schwartz
authors.forename: D
authors.initials: D
authors.lastname: Vetrie
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001766:Blindness / Q000235:genetics; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics*; D004421:Dystonia / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics; D008040:Genetic Linkage; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D011544:Pseudogenes / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D014960:X Chromosome / Q000235:genetics*
chemical_list: D011506:Proteins