Novel progranulin mutations with reduced serum-progranulin levels in frontotemporal lobar degeneration

Eur J Hum Genet. 2013 Nov;21(11):1260-5. doi: 10.1038/ejhg.2013.37. Epub 2013 Mar 6.

Abstract

Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disease with an age at onset generally below 65 years. Mutations in progranulin (GRN) have been reported to be able to cause FTLD through haploinsufficiency. We have sequenced GRN in 121 patients with FTLD and detected six different mutations in eight patients: p.Gly35Glufs*19, p.Asn118Phefs*4, p.Val200Glyfs*18, p.Tyr294*, p.Cys404* and p.Cys416Leufs*30. Serum was available for five of the mutations, where the serum-GRN levels were found to be >50% reduced compared with FTLD patients without GRN mutations. Moreover, the p.Cys416Leufs*30 mutation segregated in an affected family with different dementia diagnoses. The mutation frequency of GRN mutation was 6.6% in our FTLD cohort.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cerebral Cortex / pathology
  • Cohort Studies
  • DNA-Binding Proteins / metabolism
  • Family
  • Frontotemporal Lobar Degeneration / blood*
  • Frontotemporal Lobar Degeneration / genetics*
  • Frontotemporal Lobar Degeneration / pathology
  • Genetic Predisposition to Disease*
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / blood*
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Microsatellite Repeats / genetics
  • Mutation / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Progranulins

Substances

  • DNA-Binding Proteins
  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins