A novel X–linked gene, DDP, shows mutations in families with deafness (DFN–1), dystonia, mental deficiency and blindness

Jin, H. et al. (1996) A novel X–linked gene, DDP, shows mutations in families with deafness (DFN–1), dystonia, mental deficiency and blindness. Nature Genetics, 14(2), pp. 177-180. (doi: 10.1038/ng1096-177) (PMID:8841189)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Vetrie, Professor David
• Authors: Jin, H., May, M., Tranebjærg, L., Kendall, E., Fontán, G., Jackson, J., Subramony, S.H., Arena, F., Lubs, H., Smith, S., Stevenson, R., Schwartz, C., and Vetrie, D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Genetics
• Publisher: Nature Publishing Group
• ISSN: 1061-4036
• ISSN (Online): 1546-1718