Deletion of the progranulin gene in patients with frontotemporal lobar degeneration or Parkinson disease

Neurobiol Dis. 2008 Jul;31(1):41-5. doi: 10.1016/j.nbd.2008.03.004. Epub 2008 Apr 7.

Abstract

Progranulin gene (PGRN) mutations cause ubiquitin-positive frontotemporal lobar degeneration linked to chromosome 17 (FTLDU-17). The spectrum of known mutations strongly suggests that neurodegeneration results from a partial loss of PGRN function and leads to the hypothesis that PGRN gene deletions could be present in a subset of patients. We analysed 63 unrelated French patients with frontotemporal lobar degeneration (FTLD) for PGRN gene dosage alteration by quantitative multiplex PCR of short fluorescent fragments (QMPSF). We identified in one patient with typical PGRN neuropathology a near complete deletion, removing exons 1-11, of the PGRN gene. This deletion, which resulted from a nonhomologous recombination event, was equally present in one affected sister presenting with Parkinson disease (PD). This observation provides a final argument that PGRN mutations exert their pathogenic effect through haploinsufficiency and underlines the diversity of clinical presentations associated with these PGRN alterations.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain / pathology
  • Dementia / genetics*
  • Dementia / pathology
  • Gene Deletion*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Middle Aged
  • Neuropsychological Tests
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology
  • Pedigree
  • Polymerase Chain Reaction
  • Progranulins

Substances

  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins