Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS.
Mutations of the lipid phosphatase FIG4 that regulates PI(3,5)P(2) are responsible for the recessive peripheral-nerve disorder CMT4J. We now describe nonsynonymous variants of FIG4 in 2% (9/473) of patients with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Heterozygosity for a deleterious allele of FIG4 appears to be a risk factor for ALS and PLS, extending the list of known ALS genes and increasing the clinical spectrum of FIG4-related diseases.
Chow
Clement Y
CY
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Landers
John E
JE
Bergren
Sarah K
SK
Sapp
Peter C
PC
Grant
Adrienne E
AE
Jones
Julie M
JM
Everett
Lesley
L
Lenk
Guy M
GM
McKenna-Yasek
Diane M
DM
Weisman
Lois S
LS
Figlewicz
Denise
D
Brown
Robert H
RH
Meisler
Miriam H
MH
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D005420:Flavoproteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D016472:Motor Neuron Disease / Q000235:genetics; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases
D005420:Flavoproteins; C522215:FIG4 protein, human; D010744:Phosphoric Monoester Hydrolases