Abstract
The spinocerebellar ataxias (SCA) are a genetically and clinically heterogeneous group of diseases, characterized by dominant inheritance, progressive cerebellar ataxia and diverse extracerebellar symptoms. A subgroup of the ataxias is caused by unstable CAG-repeat expansions in their respective genes leading to pathogenic expansions of polyglutamine stretches in the encoded proteins. In general, unstable CAG repeats have an uninterrupted CAG repeat, whereas stable CAG repeats are either short or interrupted by CAA codons, which – like CAG codons – code for glutamine. Here we report on an infantile SCA2 patient who, due to germ-line CAG repeat instability in her father, inherited an extremely expanded CAG repeat in the SCA2 locus. Surprisingly, the expanded allele of the father was an interrupted CAG repeat sequence. Furthermore, analyses of single spermatozoa showed a high frequency of paternal germ-line repeat sequence instability of the expanded SCA2 locus.
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Acknowledgements
We would like to thank the family for participating in this study, Helle Andersen from the Laboratory of Reproductive Biology, Copenhagen University Hospital, for her assistance in isolating single spermatozoa and the Novo Nordisk Foundation and the Research Council of Rigshospitalet for funding this work.
Consent and ethics statement: Written informed consent for publication of this report was obtained from all patients alive. The study was approved by the Ethics Committee for the Copenhagen Regional Area, journal no. H-KF-328548.
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Vinther-Jensen, T., Ek, J., Duno, M. et al. Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2. Eur J Hum Genet 21, 626–629 (2013). https://doi.org/10.1038/ejhg.2012.231
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DOI: https://doi.org/10.1038/ejhg.2012.231
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