MAPT gene duplications are not a cause of frontotemporal lobar degeneration

Neurosci Lett. 2007 Aug 31;424(1):61-5. doi: 10.1016/j.neulet.2007.07.008. Epub 2007 Aug 1.

Abstract

Recurrent deletions of the 17q21.31 region encompassing the microtubule-associated protein tau (MAPT) gene have recently been described in patients with mental retardation. This region is flanked by segmental duplications that make it prone to inversions, deletions and duplications. Since gain-of-function mutations of the MAPT gene cause frontotemporal lobar degeneration (FTLD) characterized by deposition of tau protein, we hypothesize that MAPT duplication affecting gene dosage could also lead to disease. Gene dosage alterations have already been found to be involved in the etiology of neurodegenerative disorders caused by protein or peptide accumulation, such as Alzheimer's and Parkinson's diseases. To determine whether MAPT gene copy number variation is involved in FTLD, 70 patients with clinical diagnosis of FTLD and no MAPT mutation (including 12 patients with pathologically proven tau-positive FTLD) were screened by using multiplex ligation probe amplification (MLPA) with specific oligonucleotide probes. No copy number variation in the MAPT gene was observed in cases. Although our study was limited by the relatively small number of patients, it does not support the theory that chromosomal rearrangements in this region are a cause of FTLD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brain Chemistry / genetics
  • Chromosomes, Human, Pair 17 / genetics
  • DNA Mutational Analysis
  • Dementia / genetics*
  • Dementia / metabolism
  • Dementia / physiopathology
  • Female
  • Gene Dosage / genetics
  • Gene Duplication*
  • Genes, Duplicate / genetics*
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • tau Proteins / genetics*

Substances

  • Genetic Markers
  • tau Proteins