黄霜 甘钊杏 蒋玮莹 陈素琴

【摘要】目的鉴定一个常染色体显性β地中海贫血（β地贫）家系的致病性突变。方法调查一个常染色体显性β地贫家系的血液学及临床资料，提取外周血DNA并进行分子遗传学分析。并在PubMed数据库、人类血红蛋白变异和地中海贫血数据库（HbVar数据库）、人类基因突变数据库（HGMD数据库）、中国生物医学文献服务系统（SinoMed）、中国期刊全文数据库（CNKI）、万方数据知识服务平台和维普中文科技期刊数据库检索携带血红蛋白Dippie突变患者的资料进行分析。结果 该家系共4例患者，所有患者HBB基因的第127密码子均发生c383 A>G[beta127（H5）Gln>Arg]）杂合性突变，该变异即血红蛋白Dippie突变，导致患者出现典型的类中间型β地贫表型。β珠蛋白基因单倍型分析显示，c383G突变与单倍型2 [+ +]连锁。4例患者血红蛋白F表达水平相关的主要SNPs位点基因型均为HBG2 rs7482144 G/G（XmmI： ）、HBS1LMYB rs9399137 T/T和 BCL11A rs766432 A/A。4例患者均无KLF1基因的功能性變异。检索文献后共收集到3例携带血红蛋白Dieppe杂合性突变患者的资料，其中仅1例法国籍患者具有较详细的血液学表型资料，其症状亦为类中间型地贫症状。结论该常染色体显性β地贫家系的致病性突变为c383 A>G[beta127（H5）Gln>Arg]）杂合性突变。此变异导致该家系患者出现典型的类中间型β地贫表型。

【关键词】β地中海贫血；常染色体显性；血红蛋白Dippie；中国人

Molecular genetic analysis of a Chinese pedigree with dominantly inherited βthalassaemiaHuang Shuang， Gan Zhaoxing， Jiang Weiying， Chen Suqin Department of Laboratory， Panyu Hexian Memorial Hospital， Guangzhou 510530， China

Corresponding author，Chen Suqin， Email： chensq@mailsysueducn

【Abstract】ObjectiveTo identify the pathogenic mutation in a Chinese pedigree with dominantly inherited βthalassemia （βthalassemia） MethodsThe hematological and clinical data of a Chinese pedigree with βthalassemia were investigated DNA was extracted from the peripheral blood for molecular genetic analysis Clinical data of patients carrying hemoglobin Dippie （Hb Dippie） mutation were retrieved from PubMed， HbVar， HGMD， SinoMed， CNKI， Wanfang data and Chongqing Vip databases ResultsNucleotide sequencing of HBB gene revealed the heterozygosity for codon 127 （c383A>G [beta127 （H5） Gln>Arg]） in all four patients within this family This mutation， namely Hb Dippie， resulted in the phenotype of typical βthalassemia intermedia The βglobin haplotype demonstrated that c383G mutation was linked to the haplotype 2[+ +] For four patients， the genotypes of HbFassociated SNPs mainly consisted of rs7482144 G/G （XmmI： ） in HBG2， rs9399137 T/T in HBS1LMYB， rs766432 A/A in BCL11A No functional mutation of KLF1 gene was observed After literature retrieval， clinical data of three patients with Hb Dippie mutation were collected Among them， relatively complete hematological and phenotypic data were obtained in only one French patient， who was diagnosed with βthalassemia intermedia ConclusionsThe pathogenic mutation of the dominantly inherited βthalassemia is c383 A>G [beta127 （H5） Gln>Arg] heterogeneous mutation， which leads to typical phenotype of βthalassemia intermedia in this family

【Key words】βthalassemia； Autosomal dominance； Hemoglobin Dippie； Chinese

β地中海贫血（β地贫， MIM 613985）是由于β珠蛋白基因突变导致β珠蛋白肽链合成量减少或完全不合成而引起的慢性溶血性贫血，是我国南方常见的危害人民健康的单基因遗传病之一[1]。β地贫通常被认为是一种常染色体隐性遗传性疾病，因为患者只有同时获得2个突变等位基因（突变的纯合子或双重杂合子）而造成β珠蛋白肽链合成量严重减少时才会出现明显的临床症状。显性遗传性β地贫……