The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are neurodegenerative conditions that affect large motor neurons of the central nervous system. We have identified a familial juvenile PLS (JPLS) locus overlapping the previously identified ALS2 locus on chromosome 2q33. We report two deletion mutations in a new gene that are found both in individuals with ALS2 and those with JPLS, indicating that these conditions have a common genetic origin. The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs).
Yang
Y
Y
Department of Neurology, Northwestern University Medical School, Chicago, Illinois, USA.
Hentati
A
A
Deng
H X
HX
Dabbagh
O
O
Sasaki
T
T
Hirano
M
M
Hung
W Y
WY
Ouahchi
K
K
Yan
J
J
Azim
A C
AC
Cole
N
N
Gascon
G
G
Yagmour
A
A
Ben-Hamida
M
M
Pericak-Vance
M
M
Hentati
F
F
Siddique
T
T
D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
C438187:ALS2 protein, human; D017931:DNA Primers; D020662:Guanine Nucleotide Exchange Factors