Transthyretin Ala97Ser in Chinese-Taiwanese patients with familial amyloid polyneuropathy: genetic studies and phenotype expression

J Neurol Sci. 2008 Apr 15;267(1-2):91-9. doi: 10.1016/j.jns.2007.10.011. Epub 2007 Nov 26.

Abstract

Background: Transthyretin (TTR) variants of familial amyloid neuropathies (FAP) form a heterogenous group of autosomal dominantly inherited diseases. TTR gene analysis in several nationalities (Japanese, Portuguese, French, and British) has shown many distinguishing characteristics in the genotype-phenotype correlation. In Chinese, there are only a few reports of private TTR gene mutations belonging to single kindred.

Materials and methods: We collected five patients with autosomal dominant inheritant sensorimotor polyneuropathy and tissue-proved amyloid deposition. The diagnosis of FAP was established on the mutation of the TTR gene detected by direct sequencing. Haplotype analysis was conducted in four of these patients.

Results and conclusions: These five FAP patients shared an identical missense mutation, Ala97Ser, in the TTR gene. This mutation presented with a constellation of late-onset polyneuropathy, preceding carpal tunnel syndrome, and outstanding autonomic dysfunction. Heart was the most frequently involved vital organ. Haplotype analysis hinted independent origins although the numbers were limited. Our study is the first case series gathering from the Chinese-Taiwanese population. We proposed a possible hot-spot mutation of the TTR gene, Ala97Ser, in this ethnic.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Alanine / genetics
  • Alanine / metabolism
  • Amino Acid Substitution / genetics
  • Amyloid Neuropathies, Familial / ethnology
  • Amyloid Neuropathies, Familial / genetics*
  • Amyloid Neuropathies, Familial / metabolism*
  • Asian People / ethnology
  • Asian People / genetics
  • Axons / metabolism
  • Axons / pathology
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense / genetics*
  • Peripheral Nerves / metabolism*
  • Peripheral Nerves / pathology
  • Peripheral Nerves / physiopathology
  • Phenotype
  • Prealbumin / chemistry
  • Prealbumin / genetics*
  • Prealbumin / metabolism
  • Serine / genetics
  • Serine / metabolism
  • Taiwan / epidemiology
  • Wallerian Degeneration / ethnology
  • Wallerian Degeneration / genetics
  • Wallerian Degeneration / metabolism

Substances

  • Genetic Markers
  • Prealbumin
  • Serine
  • Alanine