A novel progranulin mutation causing frontotemporal lobar degeneration with heterogeneous phenotypic expression

J Alzheimers Dis. 2011;23(1):7-12. doi: 10.3233/JAD-2010-101461.

Abstract

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder characterized by behavioural disturbances and cognitive decline. Here we describe an Italian family with FTLD showing remarkable phenotypic heterogeneity. Based on low plasma levels of progranulin, we analyzed the progranulin gene (GRN) in two patients with early onset and found the novel frame-shift mutation T278SfsX7. mRNA analysis confirmed the null effect of the mutation. The patients were homozygous for H1 MAPT haplotype, a disease modifier factor that can account for early age at onset. Being predictive for GRN null mutations, plasma progranulin dosage should be included in diagnostic work-up of dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • DNA Mutational Analysis
  • Enzyme-Linked Immunosorbent Assay / methods
  • Family Health
  • Female
  • Frontotemporal Lobar Degeneration / diagnostic imaging
  • Frontotemporal Lobar Degeneration / genetics*
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Phenotype
  • Progranulins
  • Tomography, Emission-Computed, Single-Photon / methods
  • Tomography, X-Ray Computed / methods
  • tau Proteins / genetics

Substances

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