Abstract
Senataxin mutations are the molecular basis of two distinct syndromes: (1) ataxia oculomotor apraxia type 2 (AOA2) and (2) juvenile amyotrophic lateral sclerosis 4 (ALS4). The authors describe clinical and molecular genetic studies of mother and daughter who display symptoms of cerebellar ataxia/atrophy, oculomotor defects, and tremor. Both patients share Senataxin mutations N603D and Q653K in cis (N603D–Q653K), adjacent to an N-terminal domain thought to function in protein–protein interaction. The N-terminal and helicase domains appear to harbor missense mutation clusters associated with AOA2 and ALS4. Working synergistically, the N603D–Q653K mutations may confer a partial dominant negative effect, acting on the senataxin N-terminal, further expanding the phenotypic spectrum associated with Senataxin mutations.
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Acknowledgements
The authors would like to thank the patients for their participation. They thank Dr. Maria-Ceu Moreira for advice and constructive criticism of the manuscript. This research was supported by the National Institutes of Health (R01-1 NS42810-01) (P. F. C).
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Bassuk, A.G., Chen, Y.Z., Batish, S.D. et al. In cis autosomal dominant mutation of Senataxin associated with tremor/ataxia syndrome. Neurogenetics 8, 45–49 (2007). https://doi.org/10.1007/s10048-006-0067-8
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DOI: https://doi.org/10.1007/s10048-006-0067-8