Homozygous MAPT R406W mutation causing FTDP phenotype: A unique instance of a unique mutation

Gene. 2015 Oct 1;570(1):150-2. doi: 10.1016/j.gene.2015.06.033. Epub 2015 Jun 15.

Abstract

Frontotemporal dementia is a neurodegenerative disorder among adults. An autosomal-dominantly form of frontotemporal dementia and parkinsonism linked to chromosome 17q21.2 (FTDP-17) was defined in 1996. The MAPT gene is responsible for the major cases of FTDP-17, and tau also has a role in Alzheimer's disease. So far, different FTDP-17 causing mutations have been identified in the MAPT gene. Among different MAPT mutations, the R406W mutation has been reported with a phenotype resembling Alzheimer's disease. Nonetheless, in this study we have identified the first homozygous case of R406W mutation in an Iranian family which shows characteristics of FTDP, just like the other heterozygous mutations of MAPT. This study clearly indicates that homozygous R406W mutation could result in FTDP phenotype. Our family confirms heterogeneity in the clinical phenotype of MAPT mutations; moreover, in the R406W mutation, a dosage effect is likely to contribute to this clinical heterogeneity.

Keywords: Alzheimer's disease; MAPT; Parkinsonism; frontotemporal dementia.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Base Sequence
  • Consanguinity
  • DNA Mutational Analysis
  • Female
  • Frontotemporal Dementia / diagnosis*
  • Frontotemporal Dementia / genetics
  • Genetic Association Studies
  • Homozygote
  • Humans
  • Male
  • Mutation, Missense
  • Pedigree
  • Phenotype
  • tau Proteins / genetics*

Substances

  • MAPT protein, human
  • tau Proteins