A novel 10-base pair insertion mutation in exon 5 of the SOD1 gene in a Chinese family with amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is an adult-onset, progressive, fatal neurodegenerative disease. Several genes are associated with ALS. Copper-zinc superoxide dismutase 1 (SOD1) is one of the most commonly mutated genes in ALS, and more than 160 mutations in SOD1 have been reported. We reported a novel heterozygous insertion mutation that led to a frameshift and a premature termination at position 136 in exon 5 of the SOD1 gene (c.392_393insGCAAAGGTGG; p.N132Qfs*5) in a Chinese familial ALS pedigree. This mutation in the pedigree demonstrated an autosomal dominant pattern of inheritance and a phenotype characterized by an early onset (approximately 34 years old) with a relatively rapid course (approximately 2 years) and limb onset with respiratory involvement. The clinical feature of the p.N132Qfs*5 mutation was nearly identical to a previously reported mutation (Gly127insTGGG). Experiments in G127X mice demonstrated that the G127X mutation was pathogenic. SOD1 activity in the p.N132Qfs*5 mutation carriers in the family decreased significantly compared with normal family members. In conclusion, we identified a novel SOD1 mutation in an ALS family, which is an important addition to the catalog of SOD1 mutations in ALS.
Department of Neurology, Chinese PLA General Hospital, Beijing, China.
Siyu
S
Chen
Department of Neurology, Chinese PLA General Hospital, Beijing, China.
Mao
M
Li
Department of Neurology, Chinese PLA General Hospital, Beijing, China.
Wenjia
W
Zhu
Beijing Institutes of Life Science Chinese Academy of Science, Beijing, China; University of Chinese Academy of Science, Beijing, China.
Fengbiao
F
Mao
Beijing Institutes of Life Science Chinese Academy of Science, Beijing, China; University of Chinese Academy of Science, Beijing, China.
Jiesi
J
Wang
Beijing Institutes of Life Science Chinese Academy of Science, Beijing, China; University of Chinese Academy of Science, Beijing, China. Electronic address: zsunusa@yahoo.com.
Zhongsheng
Z
Sun
Department of Neurology, Chinese PLA General Hospital, Beijing, China. Electronic address: lewish301@sina.com.
Xusheng
X
Huang
D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D020029:Base Pairing / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D016254:Mutagenesis, Insertional / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D000072105:Superoxide Dismutase-1 / Q000235:genetics*
C000606290:SOD1 protein, human; D000072105:Superoxide Dismutase-1
ALS; Insertion mutation; SOD1