Screening of mutations in superoxide dismutase 1 gene in Chinese with familiar amyotrophic lateral sclerosis / 中华神经科杂志

Objective To identify the mutations in Cu/Zn superoxide dismutase ( SOD1 ) gene in three Chinese kindreds with amyotrophic lateral sclerosis ( ALS), compare the genotypes with those found in other ethnic groups and to analyze the clinical characteristics.Methods The diagnosis of ALS met El Escorial ALS diagnostic criteria.Genomic DNA was extracted from peripheral blood in ALS patients using standard procedure.PCR amplifications of five exons of SOD1 were performed using primers as described in the previous publication.The PCR products were directly sequenced.Results A heterozygous mutation H46R was found in four affected members in a family with middle age onset and slowly progressive ALS.A heterozygous mutation of G72C was identified in a 20-year-old male who died of respiratory failure after two years of ALS.His father carried the same mutation without clinical phenotype.In the third family with 20affected members with middle age onset and rapidly progress, a mutation of E13V was identified in 5 affected subjects.Conclusions This study is the first large screening of SOD1 mutation in Chinese familiar ALS patients.H46R has previously been found only in Japanese and Pakistanis; this is the first report in Chinese, suggesting H46R may be specific to Asians.The family with mutation G72C presented decreased penetrance, therefore screening SOD1 mutation in sporadic cases and unaffected family members is necessary.E133V is the first reported mutation and needs more study to investigate its effect on the disease.

Single nucleotide polymorphism associated with Chinese sporadic amyotrophic lateral sclerosis patient / 中华神经科杂志

Objective Amyotrophic lateral sclerosis(ALS)is a progressive paralytic disorder resulting from the degeneration of upper and lower motor neurons.Sporadic ALS(SALS)accounm for majority of patients.ALS is a kind of complex disorder.There were several single nucleotide polymorphism (SNP)reported to be associated with SALS in recently published genome-wide association(GWA)study,but there are few data from Asia ALS population and no report focus on SNP which may associated with SALS of Chinese origin.Our study is to screen and add the SNPs related to the risks of SALs in Chinese.Methods Eighty-six individuals with SALS and 94 matched controls were recruited for our study and genomic DNA from blood samples was extracted.Genotypes were determined by a matrix assisted laser desorption/ionization time of flisht mass spectrometry based approach followed by association analysis. Results Individual genotype data for 8 SNPs,rs6700125,rs10260404, rs1942239,rs2279812,rs2405657,rs558889,rs6922711 and rs935 1470 in Chinese population showed no significant association with sporadic ALS.Combining genotype data from published GWA,rs1942239 gained in strength of allelic association(P value decreased to 9.07×10-5 from 1.48×10-4),and rs558889 deviated Hardy-Weinberg equilibrium at ALS case group which may be associated with susceptibility.Conclusions SNP rs1942239 and rs558889 may contribute to susceptibility of sporadic ALS in Chinese patient.The larger sample studies are warranted to confirm the association.

Association between DPP6 polymorphism and the risk of sporadic amyotrophic lateral sclerosis in Chinese patients / 中华神经科杂志

Objective To investigate whether the polymorphism of rs10260404 in DPP6 gene in Chinese Han origin is associated with sporadic amyotrophic lateral sclerosis (SALS). Methods The genomic DNA was extracted from the leukocytes of whole blood samples in 58 Chinese Han patients with SALS and 52 healthy controls. The asymmetric PCR was processed in the presence of an unlabeled probe that contained the rs10260404 locus. The product was genotyped on light scanner and some was confirmed with sequencing. Results Two single nucleotide polymorphism, rs10260404 that was reportedly consistently strongly associated with susceptibility to SALS in different populations of European and American ancestry, rs10260404 were genotyped, but not strongly associated with ALS in Chinese patients(SALS:C:12.94%,T:87.06%;health controls:C:10.58%,T:89.43%;χ2=0.29,OR=1.256,95%CI 0.549-2.872, P>0.05). Conclusion The rs10260404 is not associated with ALS susceptibility in Chinese people.