Huntington's disease-like and ataxia syndromes: Identification of a family with a de novo SCA17/TBP mutation

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• 作者：Sara Bech ; Thor Petersen ; Anne Nø ; rremø ; lle ; Albert Gjedde ; Lise Ehlers ; Hans Eiberg ; Lena E. Hjermind ; Lis Hasholt ; Erik Lundorf ; Jø ; rgen E. Nielsen
• 关键词：HDL ; SCA ; SCA17 ; HDL4 ; TBP ; Putaminal rim hyperintensity
• 刊名：Parkinsonism and Related Disorders
• 出版年：2010
• 出版时间：January 2010
• 年：2010
• 卷：16
• 期：1
• 页码：12-15
• 全文大小：559 K

文摘

The autosomal dominant spinocerebellar ataxias, commonly referred to as SCAs, are clinically and genetically heterogeneous neurodegenerative disorders. Twenty-eight genetic subtypes have been identified, of which 7 are caused by expansion of a CAG trinucleotide repeat that encodes a polyglutamine tract in the respective proteins. SCA17 is caused by a CAG/CAA repeat expansion in the TATA box-binding protein-gene (TBP). In some cases the clinical phenotype of SCA17 overlaps that of Huntington's disease (HD), hence the use of the term Huntington's disease-like. We screened 89 patients with a Huntington's disease-like phenotype without the HD-gene mutation and 178 patients with genetically unclassified cerebellar ataxia for the mutation in TBP. A 33-year old woman presenting with an HD like phenotype with a de novo 54 CAG/CAA repeat expansion was identified. Her normal allele included 38 repeats. The patient's mother and father both carried normal range repeats, 38/38 and 33/39 respectively. Analysis of the repeat structures revealed that the expansion had occurred upon expansion of the longer paternal allele. We conclude that, however rare, SCA17 must be considered as a cause of Huntington's disease-like phenotypes and ataxia syndromes, also in isolated cases.