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

TY - JOUR

T1 - Huntington's disease-like and ataxia syndromes: identification of a family with a de novo SCA17/TBP mutation

AU - Bech, Sara

AU - Petersen, Thor

AU - Nørremølle, Anne

AU - Gjedde, Albert

AU - Ehlers, Lise

AU - Eiberg, Hans

AU - Hjermind, Lena E

AU - Hasholt, Lis

AU - Lundorf, Erik

AU - Nielsen, Jørgen E

N1 - Keywords: Adult; Ataxia; Cognition Disorders; Electroencephalography; Family Health; Female; Fluorodeoxyglucose F18; Humans; Huntington Disease; Magnetic Resonance Imaging; Male; Positron-Emission Tomography; TATA-Box Binding Protein; Temporal Lobe; Trinucleotide Repeat Expansion

PY - 2010/1

Y1 - 2010/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.parkreldis.2009.06.006

DO - 10.1016/j.parkreldis.2009.06.006

M3 - Journal article

C2 - 19595623

SN - 1353-8020

VL - 16

SP - 12

EP - 15

JO - Parkinsonism & Related Disorders

JF - Parkinsonism & Related Disorders

IS - 1

ER -