Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disorder characterized by progressive loss of upper and lower motor neurons. The clinical diagnosis is confirmed by careful history taking, neurologic examination and electromyography. Like other neurodegenerative disease, ALS has many genetic and environmental factors. There are many studies reported about the pathogenesis and treatment of ALS. Many clinical trials are currently in progress. Herein we review about the epidemiology, genetics, pathophysiology, diagnosis and treatment of ALS.
Amyotrophic Lateral Sclerosis* ; Diagnosis* ; Electromyography ; Epidemiology ; Genetics ; Motor Neurons ; Neurodegenerative Diseases ; Neurologic Examination

BACKGROUNDAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons and has no effective treatment. Recently, Iida et al. identified a single-nucleotide polymorphism (SNP) rs2275294 in the ZNF512B gene that is significantly associated with susceptibility to ALS in the Japanese population. Here, we performed a case-control study examining the possible association of rs2275294 with risk of sporadic ALS (SALS) in a large Chinese cohort.

METHODSTo assess this association, we performed a replication study in 953 SALS patients and 1039 age- and gender-matched healthy control subjects, who were recruited from Peking University Third Hospital and the First Affiliated Hospital of Anhui Medical University from January 2004 to December 2013 throughout China. We genotyped the rs2275294 SNP using polymerase chain reaction and direct sequencing.

RESULTSThe allele frequency of rs2275294 in ZNF512B was different between Japanese and Chinese. The association in Chinese between ALS patients and controls did not reach statistical significance (P = 0.54; odds ratio = 0.94; 95% confidence interval = 0.76-1.15).

CONCLUSIONSThe SNP rs2275294 in ZNF512B is not considered to be associated with ALS susceptibility in the Chinese population. Our study highlights genetic heterogeneity in ALS susceptibility in different population. Given our negative results, further replication study involving larger and more homogeneous samples in different ethnicities should be performed in the future.

Adult ; Amyotrophic Lateral Sclerosis ; epidemiology ; genetics ; Asian Continental Ancestry Group ; genetics ; Carrier Proteins ; genetics ; Case-Control Studies ; China ; epidemiology ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics

PURPOSE: The association between survivor motor neuron (SMN) gene deletion and spinal muscular atrophy suggests that sporadic amyotrophic lateral sclerosis (sALS) may be related to SMN deletion. We examined the association between the SMN genotype and susceptibility to and severity of sALS. MATERIALS AND METHODS: We genotyped the copy number of SMN1 and SMN2 in 25 patients diagnosed with sporadic ALS and 100 healthy subjects in a Korean population. Onset age and medical research council (MRC) scale were compared among patients according to SMN1 : SMN2 genotypes. RESULTS: There was a significantly higher incidence of homozygous deletion of SMN2 (SMN1 : SMN2 genotype, 2 : 0) in sALS patients (20%) than in the normal controls (2%) (p<0.001). The onset age for patients with homozygous deletion of SMN2 (2 : 0) was significantly younger (34+/-15.38 years) than that of patients with 2 : 1, 2 : 2 and 2 : 3 of the SMN1 : SMN2 genotype (59.5+/-5.09; 52.69+/-16.46 and 50+/-0.00 years) (p=0.049). The ratio of patients with an MRC scale above G4- was smaller in the 2 : 0 genotype (40%) than in the 2 : 1, 2 : 2 and 2 : 3 genotypes (83.3%, 100% and 100%) (p=0.02). CONCLUSION: The homozygous SMN2 deletion (2 : 0) was statistically more frequent and associated with earlier onset age and lower MRC scale in Korean sALS patients. These suggest that SMN2 deletion may be one of the factors associated with susceptibility to and severity of sALS in a Korean population.
Adolescent ; Adult ; Age of Onset ; Amyotrophic Lateral Sclerosis/*epidemiology/*genetics ; Asian Continental Ancestry Group/*genetics/*statistics & numerical data ; Gene Deletion ; Homozygote ; Humans ; Middle Aged ; Republic of Korea/epidemiology ; Risk Factors ; Survival of Motor Neuron 2 Protein/genetics ; Young Adult