Abstract
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).
Publication types
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Amino Acid Sequence
- Amyotrophic Lateral Sclerosis / genetics*
- Base Sequence
- Cloning, Molecular
- DNA Primers
- Female
- Genes, Recessive*
- Genetic Linkage
- Guanine Nucleotide Exchange Factors / chemistry
- Guanine Nucleotide Exchange Factors / genetics*
- Humans
- Male
- Molecular Sequence Data
- Mutation*
- Pedigree
- Reverse Transcriptase Polymerase Chain Reaction
- Sequence Homology, Amino Acid
- Signal Transduction
Substances
- ALS2 protein, human
- DNA Primers
- Guanine Nucleotide Exchange Factors
Associated data
- GENBANK/AB046783
- GENBANK/AC007242
- GENBANK/AC007279
- GENBANK/AC018615
- GENBANK/AF391100
- GENBANK/AI243773
- GENBANK/AK014320
- GENBANK/AK023024
- GENBANK/AU125528
- GENBANK/AW867853
- GENBANK/AW905587
- GENBANK/AW905617
- GENBANK/BE003282
- GENBANK/BE006110
- GENBANK/BE082284
- GENBANK/BE535882
- GENBANK/BF993329