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

Sara Bech, Thor Petersen, Anne Nørremølle, Albert Gjedde, Lise Ehlers, Hans Eiberg, Lena E. Hjermind, Lis Hasholt, Erik Lundorf, Jørgen E. Nielsen

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)12-15
Number of pages4
JournalParkinsonism and Related Disorders
Volume16
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Fingerprint

TATA-Box Binding Protein
Huntington Disease
Ataxia
Mutation
Genes
Phenotype
Alleles
Spinocerebellar Ataxias
Trinucleotide Repeats
Cerebellar Ataxia
Fathers
Neurodegenerative Diseases
Huntington Disease-Like Syndrome
Reference Values
Mothers

Keywords

  • HDL
  • HDL4
  • Putaminal rim hyperintensity
  • SCA
  • SCA17
  • TBP

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Clinical Neurology
  • Neurology

Cite this

Huntington's disease-like and ataxia syndromes : Identification of a family with a de novo SCA17/TBP mutation. / Bech, Sara; Petersen, Thor; Nørremølle, Anne; Gjedde, Albert; Ehlers, Lise; Eiberg, Hans; Hjermind, Lena E.; Hasholt, Lis; Lundorf, Erik; Nielsen, Jørgen E.

In: Parkinsonism and Related Disorders, Vol. 16, No. 1, 01.2010, p. 12-15.

Research output: Contribution to journalArticle

Bech, S, Petersen, T, Nørremølle, A, Gjedde, A, Ehlers, L, Eiberg, H, Hjermind, LE, Hasholt, L, Lundorf, E & Nielsen, JE 2010, 'Huntington's disease-like and ataxia syndromes: Identification of a family with a de novo SCA17/TBP mutation', Parkinsonism and Related Disorders, vol. 16, no. 1, pp. 12-15. https://doi.org/10.1016/j.parkreldis.2009.06.006
Bech, Sara ; Petersen, Thor ; Nørremølle, Anne ; Gjedde, Albert ; Ehlers, Lise ; Eiberg, Hans ; Hjermind, Lena E. ; Hasholt, Lis ; Lundorf, Erik ; Nielsen, Jørgen E. / Huntington's disease-like and ataxia syndromes : Identification of a family with a de novo SCA17/TBP mutation. In: Parkinsonism and Related Disorders. 2010 ; Vol. 16, No. 1. pp. 12-15.
@article{76eb34ee865849c3998da2f2cacc147a,
title = "Huntington's disease-like and ataxia syndromes: Identification of a family with a de novo SCA17/TBP mutation",
abstract = "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.",
keywords = "HDL, HDL4, Putaminal rim hyperintensity, SCA, SCA17, TBP",
author = "Sara Bech and Thor Petersen and Anne N{\o}rrem{\o}lle and Albert Gjedde and Lise Ehlers and Hans Eiberg and Hjermind, {Lena E.} and Lis Hasholt and Erik Lundorf and Nielsen, {J{\o}rgen E.}",
year = "2010",
month = "1",
doi = "10.1016/j.parkreldis.2009.06.006",
language = "English (US)",
volume = "16",
pages = "12--15",
journal = "Parkinsonism and Related Disorders",
issn = "1353-8020",
publisher = "Elsevier BV",
number = "1",

}

TY - JOUR

T1 - Huntington's disease-like and ataxia syndromes

T2 - 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.

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.

KW - HDL

KW - HDL4

KW - Putaminal rim hyperintensity

KW - SCA

KW - SCA17

KW - TBP

UR - http://www.scopus.com/inward/record.url?scp=74149089305&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=74149089305&partnerID=8YFLogxK

U2 - 10.1016/j.parkreldis.2009.06.006

DO - 10.1016/j.parkreldis.2009.06.006

M3 - Article

C2 - 19595623

AN - SCOPUS:74149089305

VL - 16

SP - 12

EP - 15

JO - Parkinsonism and Related Disorders

JF - Parkinsonism and Related Disorders

SN - 1353-8020

IS - 1

ER -