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

Peethambaran Mallika Aswathy, Pushparajan Sulajamani Jairani, Sheela Kumari Raghavan, Joe Verghese, Srinivas Gopala, Priya Srinivas, Pavagada Sivasankara Mathuranath

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)218.e1-218.e3
JournalNeurobiology of Aging
Volume39
DOIs
StatePublished - Mar 1 2016

Keywords

  • Frontotemporal dementia
  • Nonsense-mediated decay
  • Null mutation
  • PGRN
  • Progranulin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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