In cis autosomal dominant mutation of Senataxin associated with tremor/ataxia syndrome.
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.
Bassuk
A G
AG
Department of Neurology, Northwestern University's Feinberg School of Medicine, Chicago, IL, USA.
Chen
Y Z
YZ
Batish
S D
SD
Nagan
N
N
Opal
P
P
Chance
P F
PF
Bennett
C L
CL
D000293:Adolescent; D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D001259:Ataxia / Q000235:genetics*; D004265:DNA Helicases; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D064251:Multifunctional Enzymes; D009154:Mutation; D010375:Pedigree; D020365:RNA Helicases / Q000235:genetics*; D013577:Syndrome; D014202:Tremor / Q000235:genetics*
D064251:Multifunctional Enzymes; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases