A novel trinucleotide repeat expansion at chromosome 3q26.2 identified by a CAG/CTG repeat expansion detection array

Hum Genet. 2006 Sep;120(2):193-200. doi: 10.1007/s00439-006-0207-0. Epub 2006 Jun 17.

Abstract

CAG/CTG repeat expansions cause at least 12 different neurological disorders, and additional disorders of this type probably exist. Using the repeat expansion detection (RED) assay, we identified an expanded CAG/CTG repeat in a 50-year-old woman with an autosomal dominant syndrome with prominent progressive sensory neuropathy. The expansion could not be accounted for by any of the CAG/CTG repeats known to undergo expansion. To identify the locus of the expansion, we created a PCR array to assess the repeat length of all repeats of eight or more CAG or CTG triplets in the human genome. The expansion was localized to a repeat contained in an intron of a Genscan-predicted gene, 185 nt downstream of a predicted exon that is conserved through mouse. The closest experimentally verified gene in the region (TNIK, encoding a serine/threonine kinase) occurs approximately 63 Kb downstream from the repeat. The length of the expansion in the proband is 98 triplets. This repeat is not expanded in the proband's cousin (the only other affected family member for whom DNA is currently available) and no expansions were detected in a set of 230 patients with movement disorders of unknown cause. An expanded allele containing 58 triplets was detected in a single control individual, and no other expansions were detected in a set of 255 controls. The normal repeat length ranges from 5 to 30 triplets, with 8 triplets the most common allele. Our results suggest that this new repeat expansion is probably not the direct cause of the phenotype in the proband. Whether the repeat contributes to the patient's phenotype, or is associated with another phenotype, remains to be determined.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Animals
  • Chromosomes, Human, Pair 3*
  • Conserved Sequence
  • Exons
  • Female
  • Genes, Dominant
  • Genotype
  • Hereditary Sensory and Motor Neuropathy / genetics*
  • Humans
  • Introns
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Pedigree
  • Phenotype
  • Polymerase Chain Reaction
  • Spinocerebellar Ataxias / genetics
  • Trinucleotide Repeat Expansion*