In cis autosomal dominant mutation of Senataxin associated with tremor/ataxia syndrome

Authors: Bassuk, A.; Chen, Y.; Batish, S.; Nagan, N.; Opal, P.; Chance, P.; Bennett, C.

Source: Neurogenetics, Volume 8, Number 1, January 2007 , pp. 45-49(5)

Publisher: Springer

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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.

Keywords: ALS4; AOA2; Ataxia; Senataxin; Sen1p; Nucleolus

Document Type: Research article

DOI: http://dx.doi.org/10.1007/s10048-006-0067-8

Affiliations: 1: Email: cbenet@u.washington.edu

Publication date: 2007-01-01