A clinical, molecular genetics and pathological study of a FTDP-17 family with a heterozygous splicing variant c.823-10G>T at the intron 9/exon 10 of the MAPT gene

Neurobiol Aging. 2021 Oct:106:343.e1-343.e8. doi: 10.1016/j.neurobiolaging.2021.05.010. Epub 2021 May 23.

Abstract

We report the first clinical-radiological-genetic-molecular-pathological study of a kindred with c.823-10G>T MAPT intronic variant (rs63749974) associated with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We describe the clinical spectrum within this family and emphasize the association between MAPT gene variants and motor neuron disease. This report of a second family with FTDP-17 associated with c.823-10G>T MAPT variant strongly supports pathogenicity of the variant and confirms it is a 4-repeat (4R) tauopathy. This intronic point mutation, probably strengthens the polypyrimidine tract and alters the splicing of exon 10 (10 nucleotides into intron 9) close to the 3' splice site.

Keywords: Frontotemporal dementia; Genetics; Intron 9/exon 10 mutation; Neuropathology; c.823-10G>T.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain / diagnostic imaging
  • Chromosomes, Human, Pair 17 / genetics
  • Exons / genetics*
  • Female
  • Frontotemporal Dementia / diagnostic imaging
  • Frontotemporal Dementia / genetics*
  • Frontotemporal Dementia / pathology
  • Genetic Association Studies / methods*
  • Heterozygote*
  • Humans
  • Introns / genetics*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Motor Neuron Disease / genetics
  • Neuroimaging
  • Parkinsonian Disorders / diagnostic imaging
  • Parkinsonian Disorders / genetics*
  • Parkinsonian Disorders / pathology
  • Point Mutation / genetics*
  • Tauopathies / genetics
  • tau Proteins / genetics*

Substances

  • MAPT protein, human
  • tau Proteins