HLA⁃A基因三倍体家庭的分子遗传学研究———附1例报道

Molecular genetics research of a Chinese family carrying triple HLA⁃A alleles

目的研究1名预行异基因造血干细胞移植急性髓系白血病患者及4名家庭成员HLA⁃A基因三倍体分子遗传学基础。方法运用PCR⁃NGS基因测序方法进行家庭成员HLA⁃A,⁃B,⁃C,⁃DRB1,⁃DQB1,⁃E,⁃F,⁃G位点高分辨基因分型。运用PCR⁃SBT方法复核先证者HLA⁃A位点,并进一步使用单核苷酸多态性微阵列(SNP Array)分析技术扫描染色体变异。结果先证者(二姐)携带3个HLA⁃A等位基因:A∗02∶01∶01,A∗11∶01∶01,A∗24∶02∶01。6号染色体6p22.1存在162.9 Kb片段重复:arr[hg19]6p22.1(29,803,377-29,966,301)x3。家系调查表明1条单体型携带2个HLA⁃A等位基因:A∗02∶01∶01,A∗24∶02∶01,B∗54∶01∶01,C∗01∶02∶01,DRB1∗04∶05∶01,DQB1∗04∶01∶01,E∗01∶01∶01∶03,F∗01∶01∶01,G∗01∶01∶01∶01且按照孟德尔遗传定律分离稳定遗传2代。先证者(二姐),大姐,母亲均含有该单体型。结论基因微重复导致健康先证者1条单体型携带2个HLA⁃A等位基因且稳定遗传2代。常规HLA移植配型实验室需注意此种情况并准确报告检测结果。

Objective To determine molecular basis of a rare HLA⁃A typing results carrying triple A alleles in potential allo⁃HSCT donor and her family.Methods HLA⁃A,⁃B,⁃C,⁃DRB1,⁃DQB1,⁃E,⁃F,⁃G of 5 members in the family were geno⁃typed at a high⁃resolution level using next⁃generation sequencing(NGS).HLA⁃A of probosita was re⁃checked using polymer⁃ase chain reaction⁃sequence⁃based typing(PCR⁃SBT),and SNP oligonucleotide probes(SNP⁃array)were scanned with ge⁃nomic DNA of probosita.Results There was 162.9Kb duplication in 6p22.1(29,803,377-29,966,301)of probosita who carried triple A alleles A·(·(∗))02∶01∶01,A·(·(∗))11∶01∶01,A·(·(∗))24∶02∶01.Other two family members were found to carry this haplo⁃type:A·(·(∗))02∶01∶01,A·(·(∗))24∶02∶01,B·(·(∗))54∶01∶01,C·(·(∗))01∶02∶01,DRB1·(·(∗))04∶05∶01,DQB1·(·(∗))04∶01∶01,E·(·(∗))01∶01∶01∶03,F·(·(∗))01∶01∶01,G·(·(∗))01∶01∶01∶01,which as a Mendelian gene was segregated and stably transmitted through two generations.Conclu⁃sion Tiny gene duplication induces one haplotype carries two HLA⁃A alleles in a potential healthy donor for allo⁃transplan⁃taion and stably transmits through two generations.Routine HLA typing laboratories should pay more attention to this situation and accurately report.