Mutation Analysis Of 5 Candidate Genes For One Chinese BFIC Family With A Novel Locus (Ⅳ)

BackgroundBenign familial infantile convulsions(BFIC)is a rare epileptic syndrome with the mode of autosomal dominant inheritance.BFIC is characterized by afebrile convulsions which typically start from month 3 to 12 and remit spontaneously after 2 to 5 years old.The neuroradiological and plasma biochemical examinations and interictal electroencephalogram(EEG)of the patients are usually normal.By genetic linkage analysis,three gene loci for BFIC have been mapped on chromosome 19q12-13.1,16p12-q12 and 2q24 respectively,which also confirmed the genetic heterogeneity of this syndrome.Until now,no gene responsible for BFIC has been identified.A large Chinese family with BFIC was found in Hunan province of China.Then by genome-wide screening and linkage analysis,we mapped a novel locus to a 12.4cM interval between D1S2864 and D1S2830 on chromosome 1p36.12-35.1ObjectiveIn order to clone the new disease gene for BFIC,we selected 5 candidate genes in this locus interval for mutation analysis.MothodsThrough looking up bioinformatics of all known genes in the locus interval,we used the approach of functional-candidate cloning and chosed 5 candidate genes(RPA2,PNRC3,RPL11,PTP4A2,ZNF593).By polymerase chain reaction(PCR)and DNA direct sequencing,we performed mutation analysis of the 5 genes in the Chinese family. ResultsNo mutation of the 5 candidate genes was found to cause BFIC in the family.Two single nucleotide polymorphisms(SNPs)in PTP4A2 (c.36G＞A,ⅣS5+150G＞A),one SNP in RPL11(ⅣS1-17C＞G),Five SNPs inPNRC2(ⅣS3+174C＞A,ⅣS3+339A＞G,ⅣS3+682C＞A,ⅣS3+703A＞C,ⅣS3+861G＞A)and two SNPs in ZNF593(c.177T＞C,ⅣS3+133A＞C) were detected,among which c.36G＞A andⅣS5+150G＞A in PTP4A2 were novel SNPs.Conclusions1.The five candidate genes were unlikely involved in the pathogenesis of the Chinese BFIC family with the novel BFIC locus.2.10 SNPs were found in the 5 candidate genes,among which c.36G＞A andⅣS5+150G＞A in PTP4A2 were novel SNPs.