Genetics of the SCA6 gene in a large family segregating an autosomal dominant “pure” cerebellar ataxia
- Javier García-Planellsa,c,
- Ana Cuestaa,
- Juan J Vílchezb,
- Francisco Martíneza,
- Félix Prietoa,
- Francesc Palaua,c
- aUnitat de Genètica, Hospital Universitari La Fe, Av Campanar 21, E-46009 Valencia, Spain, bServei de Neurologia, Hospital Universitari La Fe, Av Campanar 21, E-46009 Valencia, Spain, cDepartament de Genètica, Facultat de Ciències Biològiques, Universitat de València, Dr Moliner 50, Burjassot, E-46100 Valencia, Spain
- Dr Palau.
- Received 5 January 1998
- Revised 10 July 1998
Abstract
Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant cerebellar degeneration caused by the expansion of a CAG trinucleotide repeat in the CACNA1A gene. Mutations in patients are characterised by expanded alleles of between 21 and 30 repeat units and by extreme gonadal stability when transmitted from parents to children. We have investigated the SCA6 mutation in a large Spanish kindred in which previously reported spinocerebellar SCA genes and loci had been excluded. We observed a 23 CAG repeat expanded allele in the 13 clinically affected subjects and in three out of 10 presymptomatic at risk subjects. Transmission of the mutant allele was stable in six parent to child pairs and in 29 meioses through the pedigree. Linkage analysis with the SCA6-CAG polymorphism and marker D19S221 confirmed the location of SCA6 on chromosome 19p13. The molecular findings in this large family confirm the expansion of the CAG repeat in the CACNA1A gene as the cause of SCA6 and the high meiotic stability of the repeat.
