Abstract
Wereport the first de novo mutation in the DDP gene in a Dutch 11-year-old boy with deafness and dystonia. Previously reported mutations inthe DDP gene have all been frameshifts/nonsense mutations or deletion of the entire gene as part of a larger deletion encompassing the BTKgene. The clinical presentation was uniformly characterised by sensorineural hearing loss, dystonia, mental deterioration, paranoid psychotic features, and opticatrophy, indicating progressive neurodegeneration. Our report illustrates that de novo mutations occur and that a missense mutation, C66W, may causean equally severe clinical picture. The diagnosis of sensorineural hearing impairment associated with neurologic and visual disability in a male, therefore, shouldencourage the search for mutations in the DDP gene, even in sporadic cases. The association of deafness–dystonia syndrome with a missensemutation provides valuable information for in vitro investigations of the functional properties of the deafness–dystonia peptide which wasrecently shown to be the human homolog of a yeast protein, Tim8p, belonging to a family of small Tim proteins involved in intermembrane protein transport inmitochondria.
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Tranebjærg, L., Hamel, B., Gabreels, F. et al. A de novo missense mutation in a critical domain of the X-linked DDP gene causes the typical deafness–dystonia–optic atrophy syndrome. Eur J Hum Genet 8, 464–467 (2000). https://doi.org/10.1038/sj.ejhg.5200483
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DOI: https://doi.org/10.1038/sj.ejhg.5200483
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