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Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS

Clement Y Chow1, John E Landers, Sarah K Bergren

  • 1Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.

American Journal of Human Genetics
|January 3, 2009
PubMed

Insights

Mutations in the FIG4 gene, previously linked to CMT4J, are found in some patients with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). This suggests FIG4 variants are a risk factor for these neurodegenerative diseases.

Area of Science:

  • Neurogenetics
  • Molecular Biology
  • Cellular Biology

Background:

  • The lipid phosphatase FIG4 regulates PI(3,5)P(2) and its mutations cause the peripheral neuropathy CMT4J.
  • Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are progressive neurodegenerative conditions affecting motor neurons.

Purpose of the Study:

  • To investigate the role of FIG4 gene variants in patients diagnosed with ALS and PLS.
  • To determine if heterozygosity for FIG4 alleles constitutes a risk factor for ALS and PLS.

Main Methods:

  • Genetic sequencing of the FIG4 gene in a cohort of patients with ALS and PLS.
  • Analysis of nonsynonymous variants identified in the FIG4 gene.

Main Results:

  • Nonsynonymous variants in the FIG4 gene were identified in 2% (9/473) of patients with ALS and PLS.
  • Deleterious alleles of FIG4 were found to be associated with an increased risk of developing ALS and PLS.

Conclusions:

  • The FIG4 gene is implicated in the pathogenesis of ALS and PLS, expanding its known clinical spectrum beyond CMT4J.
  • Genetic variations in FIG4 represent a novel risk factor for ALS and PLS, contributing to the understanding of these complex diseases.

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