Abstract
CAG repeat expansions with loss of CAT interruptions in the coding region of the ataxin-1 gene are associated with spinocerebellar ataxia type 1 (SCA1). For molecular genetic diagnosis it is necessary to define the limits of normal and pathological size ranges. In most studies, normal alleles as measured by PCR range from 6–39 units with interruptions of 1–3 CAT trinucleotides that are thought to be involved in the stability of the trinucleotide stretch during DNA replication. Expanded alleles have been reported to carry 39–81 CAG trinucleotides without stabilising CAT interruptions. To evaluate the limits between normal and disease size ranges we analysed the repeat length and composition of the SCA1 gene in 15 individuals with alleles ranging from 36 and 41 triplets for genotype-phenotype correlation studies. We found the 39 trinucleotide-allele to be either interrupted by CAT repeats or formed by a pure CAG stretch. The clinical features of individuals carrying 39 uninterrupted CAG repeats did not differ from the SCA1 phenotype in general with dysphagia, pale discs, pyramidal signs and cerebellar tremor being more frequent as compared to other SCA genotypes. In contrast, the interrupted 39 trinucleotide-allele is not correlated with the SCA1 phenotype.
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Acknowledgements
We would like to thank J Atici and U Gehlken for excellent technical help. This work was supported by the Forschungsförderungsprogramm der Medizinischen Universität Lübeck (1799/N03) and the Fritz Thyssen Stiftung, Köln (AZ 1999 2060). We thank all patients for providing blood samples for scientific research and their clinicians for collecting them. We thank the German Heredo-Ataxia Society (DHAG), whose cooperation is essential in our work.
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Zühlke, C., Dalski, A., Hellenbroich, Y. et al. Spinocerebellar ataxia type 1 (SCA1): Phenotype-genotype correlation studies in intermediate alleles. Eur J Hum Genet 10, 204–209 (2002). https://doi.org/10.1038/sj.ejhg.5200788
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DOI: https://doi.org/10.1038/sj.ejhg.5200788
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