Progranulin mutation analysis: Identification of one novel mutation in exon 12 associated with frontotemporal dementia

Neurobiol Aging. 2016 Mar:39:218.e1-3. doi: 10.1016/j.neurobiolaging.2015.11.026. Epub 2015 Dec 8.

Abstract

Progranulin (PGRN) mutations account for an average of 15% of familial frontotemporal dementia (FTD) cases and 20% of total FTD cases worldwide. Here, we investigated the frequency of PGRN mutations in FTD patients (n = 116) from a clinical cohort of south India and detected one novel mutation located on exon 12 in a familial behavioral variant FTD patient (accounting for ∼1% of total FTD cases and 6% of familial FTD cases). This mutation was found to introduce a premature termination codon and the prematurely terminated messenger RNA may probably undergo nonsense-mediated decay. In enzyme-linked immunosorbent assay, the proband showed significantly reduced level of plasma PGRN (28 ng/mL) compared with controls (150 ± 38 ng/mL), which implicates haploinsufficiency as the pathogenic mechanism.

Keywords: Frontotemporal dementia; Nonsense-mediated decay; Null mutation; PGRN; Progranulin.

Publication types

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

MeSH terms

  • Aged
  • Codon, Nonsense / genetics
  • Cohort Studies
  • DNA Mutational Analysis*
  • Enzyme-Linked Immunosorbent Assay
  • Exons / genetics*
  • Female
  • Frontotemporal Dementia / genetics*
  • Genetic Association Studies*
  • Humans
  • India
  • Intercellular Signaling Peptides and Proteins / blood
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Progranulins
  • RNA, Messenger / genetics

Substances

  • Codon, Nonsense
  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • RNA, Messenger