Nature Genetics
14, 177 - 180 (1996)
doi:10.1038/ng1096-177
A novel X−linked gene, DDP, shows mutations in families with deafness (DFN−1), dystonia, mental deficiency and blindnessHong Jin1, Melanie May2, Lisbeth Tranebjærg3, Elaine Kendall1, Gumersindo Fontán1, John Jackson5, S.H. Subramony6, Fernando Arena7, Herbert Lubs3, 7, Stephanie Smith5, Roger Stevenson2, Charles Schwartz2
& David Vetrie1, 8
1Division of Medical and Molecular Genetics, Guy's and St. Thomas's Hospitals, London, SE1 9RT, UK
2J.C. Self Research Institute, Greenwood Genetic Center, Greenwood, South Carolina, 29646 USA
3Dept. of Medical Genetics, University Hospital of TromsØ, N-9038 Tromsø, Norway
4Immunology Unit, Hospital La Paz, 28046 Madrid, Spain
5Division of Medical Genetics, Dept. of Preventive Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA
6Dept. of Neurology, University of Mississippi Medical Center, Jackson, Mississippi, USA
7Dept. of Pediatrics, Genetics Division, University of Miami, Miami, Florida, USA
8e-mail: d.vetrie@umds.ac.uk In 1960, progressive sensorineural deafness (McKu-sick 304700, DFN-1) was shown to be X-linked based on a description of a large Norwegian pedigree1 . 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-Tranebjasrg 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 (deaf-ness/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.
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