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BMC Medical Genetics

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Open Access 01-12-2005 | Research article

Spinocerebellar ataxia type 17: Report of a family with reduced penetrance of an unstable Gln₄₉TBP allele, haplotype analysis supporting a founder effect for unstable alleles and comparative analysis of SCA17 genotypes

Authors: Christine Zühlke, Andreas Dalski, Eberhard Schwinger, Ulrich Finckh

Published in: BMC Medical Genetics | Issue 1/2005

Abstract

Background

Spinocerebellar ataxia type 17 (SCA17), a neurodegenerative disorder in man, is caused by an expanded polymorphic polyglutamine-encoding trinucleotide repeat in the gene for TATA-box binding protein (TBP), a main transcription factor. Observed pathogenic expansions ranged from 43 – 63 glutamine (Gln) codons (Gln_43–63). Reduced penetrance is known for Gln_43–48 alleles. In the vast majority of families with SCA17 an expanded CAG repeat interrupted by a CAA CAG CAA element is inherited stably.

Results

Here, we report the first pedigree with a Gln₄₉ allele that is a) not interrupted, b) unstable upon transmission, and c) associated with reduced penetrance or very late age of onset. The 76-year-old father of two SCA17 patients carries the Gln₄₉ TBP allele but presents without obvious neurological symptoms. His children with Gln₅₃ and Gln₅₂ developed ataxia at the age of 41 and 50. Haplotype analysis of this and a second family both with uninterrupted expanded and unstable pathological SCA17 alleles revealed a common core genotype not present in the interrupted expansion of an unrelated SCA17 patient. Review of the literature did not present instability in SCA17 families with expanded alleles interrupted by the CAA CAG CAA element.

Conclusion

The presence of a Gln₄₉ SCA17 allele in an asymptomatic 76-year-old male reams the discussion of reduced penetrance and genotypes producing very late disease onset. In SCA17, uninterrupted expanded alleles of TBP are associated with repeat instability and a common founder haplotype. This suggests for uninterrupted expanded alleles a mutation mechanism and some clinical genetic features distinct from those alleles interrupted by a CAA CAG CAA element.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/6/27/prepub

Title: Spinocerebellar ataxia type 17: Report of a family with reduced penetrance of an unstable Gln49TBP allele, haplotype analysis supporting a founder effect for unstable alleles and comparative analysis of SCA17 genotypes
Authors: Christine Zühlke
Andreas Dalski
Eberhard Schwinger
Ulrich Finckh
Publication date: 01-12-2005
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2005
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-6-27

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Spinocerebellar ataxia type 17: Report of a family with reduced penetrance of an unstable Gln₄₉TBP allele, haplotype analysis supporting a founder effect for unstable alleles and comparative analysis of SCA17 genotypes

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

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Abstract

Background

Results

Conclusion

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