常染色体显性遗传Alport综合征一家系COL4A3及COL4A4的基因突变

Mutation analysis for COL4A3 and COL4A4 genes in an autosomal dominant Alprot syndrome family

目的:对一常染色体显性遗传Alport综合征(AS)家系COL4A3/COL4A4基因突变进行分析,寻找其致病突变位点。方法:采用PCR技术和直接测序法分析该家系先证者COL4A3/COL4A4基因全部外显子序列,并与该家系成员、50名健康个体及GenBank序列进行比较分析,筛选有意义突变。结果:在该家系COL4A3/COL4A4基因中共发现8个突变位点,其中包括1个错义突变、1个内含子突变和6个序列变异。COL4A4基因第44外显子上一个新的错义突变c.4195 A>T导致M1399L,该家系成员中患者均出现了此突变且均表现为杂合子。1个内含子突变为c.4127+11 C>T。其余6个序列变异分别为COL4A3基因上的c.1195 C>T,c.1223 G>A;以及COL4A4基因上的c.3011 C>T,c.4207 T>C,c.4548 A>G,c.4932 C>T。结论:常染色体显性遗传AS COL4A4基因c.4195 A>T和c.4127+11 C>T突变可能与其发病有关。

Aim：To find the pathogenic mutations among an autosomal dominant Alport syndrome （ AS） family.Meth-ods：All exons of COL4A3 and COL4A4 genes of proband were detected by PCR technology and direct sequencing ,and the mutations were analyzed by comparing with others in this family ,healthy individuals and GenBank sequence .Results：Total eight mutations in COL4A3/COL4A4 genes included one missense mutation ,one intron mutation and six sequence varia-tions.A novel missense mutation（c.4195 A〉T,M1399L）at 44th exon of COL4A4 was found,and this mutation showed heterozygous in all patients of this family .A novel intron mutation in c .4127＋11 C〉T was observed.Other six sequence variations included c .1195 C〉T,and c.1223 G〉A in COL4A3 gene,and c.3011 C〉T,c.4207 T〉C,c.4548 A〉G and c.4932 C〉T in COL4A4 gene.Conclusion：The novel missense mutation （ c.4195 A〉T,c.4127＋11 C〉T） maybe re-sponsible for the cause of AS in this family .