Huntington's disease-like and ataxia syndromes: identification of a family with a de novo SCA17/TBP mutation.
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.
Bech
Sara
S
Department of Cellular and Molecular Medicine, Section of Neurogenetics, The Panum Institute, University of Copenhagen, Denmark. sarabw@sund.ku.dk <sarabw@sund.ku.dk>
Petersen
Thor
T
Nørremølle
Anne
A
Gjedde
Albert
A
Ehlers
Lise
L
Eiberg
Hans
H
Hjermind
Lena E
LE
Hasholt
Lis
L
Lundorf
Erik
E
Nielsen
Jørgen E
JE
D000328:Adult; D001259:Ataxia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D004569:Electroencephalography / Q000379:methods; D005192:Family Health; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D035181:TATA-Box Binding Protein / Q000235:genetics*; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000473:pathology; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
D035181:TATA-Box Binding Protein; C509817:TBP protein, human; D019788:Fluorodeoxyglucose F18