Progranulin mutations and amyotrophic lateral sclerosis or amyotrophic lateral sclerosis-frontotemporal dementia phenotypes

J Neurol Neurosurg Psychiatry. 2007 Jul;78(7):754-6. doi: 10.1136/jnnp.2006.109553. Epub 2007 Mar 19.

Abstract

Objective: Mutations in the progranulin (PGRN) gene were recently described as the cause of ubiquitin positive frontotemporal dementia (FTD). Clinical and pathological overlap between amyotrophic lateral sclerosis (ALS) and FTD prompted us to screen PGRN in patients with ALS and ALS-FTD.

Methods: The PGRN gene was sequenced in 272 cases of sporadic ALS, 40 cases of familial ALS and in 49 patients with ALS-FTD.

Results: Missense changes were identified in an ALS-FTD patient (p.S120Y) and in a single case of limb onset sporadic ALS (p.T182M), although the pathogenicity of these variants remains unclear.

Conclusion: PGRN mutations are not a common cause of ALS phenotypes.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / complications*
  • Amyotrophic Lateral Sclerosis / genetics*
  • Cross-Sectional Studies
  • DNA Mutational Analysis
  • Dementia / etiology*
  • Dementia / genetics*
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Mutation, Missense
  • Phenotype
  • Progranulins

Substances

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