Journal Article

SCA6 is Caused by Moderate CAG Expansion in the α<sub>1A</sub>-Voltage-Dependent Calcium Channel Gene

Olaf Riess, Ludger Schöls, Heike Böttger, Dagmar Nolte, Ana Maria Menezes Vieira-Saecker, Carmen Schimming, Friedmar Kreuz, Milan Macek, Alice Krebsová, Milan Macek Sen, Thomas Klockgether, Christine Zühlke and Franco A. Laccone

in Human Molecular Genetics

Volume 6, issue 8, pages 1289-1293
Published in print August 1997 | ISSN: 0964-6906
Published online August 1997 | e-ISSN: 1460-2083 | DOI:
SCA6 is Caused by Moderate CAG Expansion in the α1A-Voltage-Dependent Calcium Channel Gene

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Recently, moderate (CAG)>20 repeat expansions in the α1A-voltage-dependent calcium channel gene (CACNL1A4) have been identified in a previously unmapped type of SCA which has been named SCA6. We investigated the (CAG)n repeat length of the CACNL1A4 gene in 733 patients with sporadic ataxia and in 46 German families with dominantly inherited SCA which do not harbor the SCA1, SCA2, or MJD1/SCA3 mutation, respectively. The SCA6 (CAG)n expansion was identified in 32 patients most frequently with late manifestation of the disease. The (CAG)n stretch of the affected allele varied between 22 and 28 trinucleotide units and is therefore the shortest trinucleotide repeat expansion causing spinocerebellar ataxia. The (CAG)n repeat length is inversely correlated with the age at onset. In 11 parental transmissions of the expanded allele no repeat instability has been observed. Repeat instability was also not found for the normal allele investigating 431 meioses in the CEPH families. Analyzing 248 apparently healthy octo-generians revealed one allele of 18 repeats which is the longest normal CAG repeat in the CACNL1A4 gene reported. The SCA6 mutation causes the disease in ∼10% of autosomal dominant SCA in Germany. Most importantly, the trinucleotide expansion was observed in four ataxia patients without obvious family history of the disease which necessitates a search for the SCA6 (CAG)n expansion even in sporadic patients.

Journal Article.  3720 words.  Illustrated.

Subjects: Genetics and Genomics

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