Detection Of FGF14 Gene Mutation In Spinocerebellar Ataxia Patients

BackgroundHereditary spinocerebellar ataxia(SCA) is a group of neurodegenerative disease which shares high clinical and genetic heterogeneity.It mainly involves the cerebellum,the brainstem and the spinal cord.The clinical phenotype mainly is cerebellar ataxia.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,17 genes responsible for the disease have been cloned,including SCA1,SCA2,MJD1,PLEKHG4,SPTBN2,CACNA1A,SCA7,ATXN80S,ATXN10,TTBK2,PPP2R2B,KCNC3,PRKCG,ITPR1,TBP,FGF14and DRPLA.The fibroblast growth factor 14(FGF14) gene is responsible for SCA27,which is a rare subtype of SCA in the world.ObjectiveTo screen for the mutation of FGF14 gene in patients with spinocerebellar ataxia(SCA) by using denaturing high performance liquid chromatography(DHPLC) and to establish FGF14 gene diagnosis method by using DHPLC. MethodsBy technology of denaturing high performance liquid chromatography(DHPLC),we detect the mutation of FGF14 gene in 67 patients with spinocerebellar ataxia(SCA) excluded from the SCA1, 2,3,6,7,12,17 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 and segregation analysis in family to make sure that whether it is a polymorphism or a mutation.ResultsAll the 5 exons of the FGF14 gene in 67 patients with SCA were detected by DHPLC.We got 402 amplicons in total.At last we found a heterozygous DNA variation(c.-10del C) resulting in a novel single-nucleotide polymorphism(SNP) in the 5'UTR region of the extron 1B.ConclusionEstablish FGF14 gene diagnosis method by using denaturing high performance liquid chromatography(DHPLC).We develop the FGF14 gene mutation analysis by DHPLC for the first time internally.We found a novel single-nucleotide polymorphism(c.- 10del C) in the 5'UTR region of the extron 1B.SCA27 is a rare subtype of SCA in China.