Detection Of KCNC3 Gene Mutation In Spinocerebellar Ataxia Patients

BackgroundHereditary spinocerebellar ataxia(SCA)is a group of neurodegenerative disease which shares high clinical and genetic heterogeneity.The common age at onset occurs at youth and adult.The clinical phenotype includes cerebellar ataxia,dysarthria,intention tremor, ophthalmoparalysis,pyramidal and(or)extrapyramidal signs.It mainly involves the cerebellum,the brainstem and the spinal cord.The pathological change is neuron loss and gliosis.Most of the patients are of an autosomal dominant inheritance trait.At least 28 genotypes of SCAs have been identified up to now.Among them,18 genes responsible for the disease have been cloned,including SCA1,SCA2,MJD1,PLEKHG4, SPTBN2,CACNA1A,SCA7,ATXN8OS,ATXN10,TTBK2,PPP2R2B, KCNC3,PRKCG,ITPR1,CNCT4,TBP,FGF14 and DRPLA.We took genetic diagnosis of SCA cases collected all previous years and excluded from SCA 1,2,3,6,7,8,10,12,17 or DRPLA in our previous research. As the genotypes of sixty-seven autosomal dominant SCA families remained unknown,we screen for the mutation of KCNC3 gene further. ObjectiveTo screen for the mutation of KCNC3 gene in patients with spinocerebellar ataxia by using denaturing high performance liquid chromatography.MethodsBy technology of DHPLC,we detect the mutation of KCNC3 gene in 67 patients with autosomal dominant SCA excluded from the SCA1,2, 3,6,7,8,10,12,17 or DRPLA previously.The amplicons with abnormal peak form detected by DHPLC were sequenced.If we find the base differentiation,we should apply the crosscheck analysis in 100 healthy persons.ResultsAll the exons of the KCNC3 gene in 67 patients with SCA were detected by DHPLC.We got 804 amplicons in total.Single peak form and coincident peak form in each group were obtained.No abnormal peak form found.ConclusionWe develop the KCNC3 gene mutation analysis by DHPLC for the first time internally.No causative mutation or single nucleotide polymorphism found temporarily.