Episodic ataxia type 2. Three novel truncating mutations and one novel missense mutation in the CACNA1A gene.
We analysed the CACNA1A gene, located on chromosome 19p13, in three unrelated families and one sporadic case with episodic ataxia type 2 (EA-2). In two of the families and the sporadic patient, novel truncating mutations, which disrupt the reading frame and result in a premature stop of the CACNA1A protein, were identified in exons 14, 16 and 26. In the remaining family, a novel missense mutation (H253Y) was found. Of the twenty two EA-2 mutations identified thus far, including those of the present study, seventeen are truncating mutations and five are missense mutations, all resulting in an EA-2 clinical phenotype.
van den Maagdenberg
A M J M
AM
MGC-Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
Kors
E E
EE
Brunt
E R
ER
van Paesschen
W
W
Pascual
J
J
Ravine
D
D
Keeling
S
S
Vanmolkot
K R J
KR
Vermeulen
F L M G
FL
Terwindt
G M
GM
Haan
J
J
Frants
R R
RR
Ferrari
M D
MD
D000328:Adult; D000595:Amino Acid Sequence / Q000235:genetics; D015220:Calcium Channels / Q000172:deficiency* / Q000235:genetics*; D020865:Calcium Channels, P-Type / Q000172:deficiency* / Q000235:genetics*; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D006639:Histidine / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D017434:Protein Structure, Tertiary / Q000235:genetics; D013132:Spinocerebellar Degenerations / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; D020865:Calcium Channels, P-Type; D006639:Histidine; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type