Small de novo duplication in the repeat region of the TATA-box-binding protein gene manifest with a phenotype similar to variant Creutzfeldt-Jakob disease

A Shatunov, E A Fridman, F I Pagan, J Leib, A Singleton, M Hallett, L G Goldfarb

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

A 20-year-old North American patient developed rapidly progressive cognitive decline and pronounced ataxia, a phenotype compatible with prion disease. No structural changes were found in the PRNP gene, which excludes genetic prion disease, but the patient's PRNP codon 129 Met/Met genotype is known to predispose to variant Creutzfeldt-Jakob disease (vCJD). Further studies identified an expanded allele with 55 CAG/CAA repeats in the TBP gene. The increase of trinucleotide repeat number in the coding region of the TBP gene has previously been associated with spinocerebellar ataxia type 17 (SCA17). The patient's unaffected parents and siblings show normal-size TBP alleles with 37-38 repeats. Haplotype and nucleotide sequence analyses clearly indicate that the mutation has occurred de novo on a paternal chromosome by insertion/duplication of a (CAA)(CAG)(CAA)(CAG)(15) sequence. This report presents a second fully investigated sporadic case of SCA17 occurring as a result of a DNA rearrangement within the polymorphic TBP trinucleotide repeat region. Our findings suggest that patients suspected of vCJD should undergo testing for SCA17, Huntington's disease and other neurodegenerative disorders having phenotypic similarities with vCJD.

Original languageEnglish
Pages (from-to)496-501
Number of pages6
JournalClinical Genetics
Volume66
Issue number6
DOIs
Publication statusPublished - Dec 2004

Keywords

  • Adult
  • Amyloid
  • Chromosomes, Human, Pair 6
  • Creutzfeldt-Jakob Syndrome
  • Female
  • Haplotypes
  • Humans
  • Mutation
  • Pedigree
  • Phenotype
  • Prion Proteins
  • Prions
  • Protein Precursors
  • Spinocerebellar Ataxias
  • TATA-Box Binding Protein
  • Trinucleotide Repeat Expansion
  • Case Reports
  • Journal Article

Fingerprint

Dive into the research topics of 'Small de novo duplication in the repeat region of the TATA-box-binding protein gene manifest with a phenotype similar to variant Creutzfeldt-Jakob disease'. Together they form a unique fingerprint.

Cite this