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PMID: 11586298 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2.

Nature genetics ·Vol. 29 ·No. 2 ·2001-10-00 ·Pages 166-73

Hadano S, Hand CK, Osuga H, Yanagisawa Y, Otomo A, Devon RS, Miyamoto N, Showguchi-Miyata J, Okada Y, Singaraja R, Figlewicz DA, Kwiatkowski T, Hosler BA, Sagie T, Skaug J, Nasir J, Brown RH, Scherer SW, Rouleau GA, Hayden MR, Ikeda JE

Abstract

Amyotrophic lateral sclerosis 2 (ALS2) is an autosomal recessive form of juvenile ALS and has been mapped to human chromosome 2q33. Here we report the identification of two independent deletion mutations linked to ALS2 in the coding exons of the new gene ALS2. These deletion mutations result in frameshifts that generate premature stop codons. ALS2 is expressed in various tissues and cells, including neurons throughout the brain and spinal cord, and encodes a protein containing multiple domains that have homology to RanGEF as well as RhoGEF. Deletion mutations are predicted to cause a loss of protein function, providing strong evidence that ALS2 is the causative gene underlying this form of ALS.

MeSH Terms

Amino Acid Sequence Amyotrophic Lateral Sclerosis/genetics Animals Chromosome Mapping Chromosomes, Human, Pair 2 Female GTP Phosphohydrolases/metabolism Guanine Nucleotide Exchange Factors/chemistry,genetics Humans Male Mice Molecular Sequence Data Mutation Polymorphism, Genetic Sequence Homology, Amino Acid

Chemicals

ALS2 protein, human Guanine Nucleotide Exchange Factors GTP Phosphohydrolases

Authors & Affiliations

21 authors, click to expand affiliations / ORCID

Hadano S

NeuroGenes, International Cooperative Research Project, Japan.

Hand C K

Osuga H

Yanagisawa Y

Otomo A

Devon R S

Miyamoto N

Showguchi-Miyata J

Okada Y

Singaraja R

Figlewicz D A

Kwiatkowski T

Hosler B A

Sagie T

Skaug J

Nasir J

Brown R H

Scherer S W

Rouleau G A

Hayden M R

Ikeda J E

Article Info

Journal

Nature genetics

Abbr.

Nat Genet

ISSN

1061-4036

DOI

10.1038/ng1001-166

Published

2001-10-00

Pages

166-73

Language

English

Region

United States

NLM ID

9216904

Subset

Databases

GENBANK

AB053301, AB053302, AB053303, AB053304, AB053305, AB053306, AB053307, AB053308, AB053309, AB053310, AB053311, AB053312, AB053313, AB053314, AB053315, AB053316, AB053317, AB053318, AB053319, AB053320, AB053321

Corrections

CommentIn

PMID: 11586285

External Links

PubMed source DOI: 10.1038/ng1001-166 View journal details

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A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2.

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