A de novo missense mutation in a critical domain of the X-linked DDP gene causes the typical deafness-dystonia-optic atrophy syndrome

被引:57
作者
Tranebjærg, L [1 ]
Hamel, BCJ
Gabreels, FJM
Renier, WO
Van Ghelue, M
机构
[1] Univ Tromso Hosp, Dept Med Genet, N-9038 Tromso, Norway
[2] Univ Nijmegen Hosp, Dept Human Genet, Div Clin Genet, Nijmegen, Netherlands
[3] Univ Nijmegen Hosp, Dept Child Neurol, Nijmegen, Netherlands
关键词
DDP gene; mitochondrial dysfunction; dystonia; hearing impairment;
D O I
10.1038/sj.ejhg.5200483
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We report the first de novo mutation in the DDP gene in a Dutch Ii-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.
引用
收藏
页码:464 / 467
页数:4
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