Variants in the ALS2 gene are not associated with sporadic amyotrophic lateral sclerosis
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Amyotrophic lateral sclerosis (ALS) is a degenerative disease of motor neurons characterized by progressive paralysis leading to death, usually within 3–5 years. About 10% of cases are familial and autosomal dominant. Until recently, only one gene (Cu/Zn superoxide dismutase or SOD1) was known to be mutated in ALS, with mutations accounting for 20% of familial cases . For sporadic cases, various studies have shown between 2% and 7% have mutations in SOD1 [2, 3]. A recessive form of the disease with onset usually by the early teens, prominent corticobulbar and corticospinal involvement, and slow progression was recently associated with mutations in a novel ALS2 gene on chromosome 2 [4, 5]. Seven mutations have been reported so far, initially in inbred families, but more recently also from families with no apparent consanguinuity. This, coupled with the knowledge that SOD1 mutations may be a cause of sporadic disease, has led to speculation that compound heterozygosity for ALS2...
KeywordsAmyotrophic lateral sclerosis ALS2 gene Alsin Association study DNA pooling
A.A.C. is a Medical Research Council (MRC) Clinician Scientist. V.H. is funded by the MRC. C.S. is funded by GKT Medical School. We wish to thank the Motor Neurone Disease Association, Muscular Dystrophy Association, Project ALS, ALS Association, and the Angel Fund. R.B. also receives generous funding from the National Institutes of Health (NINDS and NIA).
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