一例β-地中海贫血病例中罕见基因突变的鉴定  

Identification of rare gene mutations in a case ofβ-thalassemia

作　　者：陈扬[1] 王婵 冯女 刘海芳[1] 唐小燕 张淑芳[1] CHEN Yang;WANG Chan;FENG NYU;LIU Haifang;TANG Xiaoyan;ZHANG Shufang(Central Laboratory,Affiliated Haikou Hospital of Xiangya Medical College,Central South University,Haikou,Hainan 570208,China)

机构地区：[1]中南大学湘雅医学院附属海口医院中心实验室,海南海口570208

出　　处：《中国热带医学》2020年第6期548-551,共4页China Tropical Medicine

基　　金：海南省重大科技项目(No.ZDKJ2017007);海南省医药卫生科研项目基金(No.18A200055);海口市人民医院院内课题(No.2017-YNK-20)。

摘　　要：目的对海口市人民医院血液科一例47岁男性经临床检查存在贫血、脾大等症状的疑似β地中海贫血的先证者进行病因确诊,并对其家系成员进一步研究分析。方法采用血常规、脾脏B超、血红蛋白电泳、跨越断点PCR(Gap-PCR)和高通量测序(next generation sequencing,NGS)技术对先证者和5名家系成员进行检测,评估他们贫血、脾脏肿大和基因突变等方面的情况,采用Sanger测序法对高通量测序所检测出的基因突变进行验证,并通过家系连锁分析确定所检测基因突变的遗传方式。结果先证者同时检测出HBB:c.2T>G和HBB:c.-113A>G两种突变,其中HBB:c.2T>G为常见β突变,HBB:c.-113A>G为新的突变,其母亲及儿子均检出HBB:c.-113A>G杂合突变,其女儿检出HBB:c.2T>G杂合突变,除先证者外其他家系成员并未表现出明显的地贫症状。结论HBB:c.2T>G杂合复合HBB:c.-113A>G杂合突变会加重β地贫的临床表现,进而表现出脾大症状,该基因突变的发现,丰富了地贫基因突变数据库。全面的检测技术应用于地贫常规检测对临床病人的病因确诊、治疗和遗传咨询都具有重要意义。Objective A 47-year-old male proband suspected ofβ-thalassemia with symptoms such as anemia and splenomegaly was diagnosed by clinical examination in the Department of Hematology,Affiliated Haikou Hospital of Xiangya Medical College,and his family members were further studied and analyzed.Methods The proband and 5 family members were detected by blood routine,spleen B-ultrasound,hemoglobin electrophoresis,Gap-PCR and high-throughput sequencing(NGS)to evaluate their anemia,splenomegaly and gene mutation.Sanger sequencing was used to verify the gene mutation detected by high-throughput sequencing.The genetic mode of the detected gene mutation was determined by pedigree linkage analysis.Results The proband detected both HBB:c.2T>G and HBB:c.-113A>G mutations,in which HBB:c.2T>G was a commonβmutation,HBB:c.-113A>G was a new mutation,HBB:c.-113>G heterozygous mutation was detected in both his mother and son,and HBB:c.2T>G heterozygous mutation was detected in his daughter.Except for the proband,other family members did not show obvious symptoms of thalassemia.Conclusions HBB:c.2T>G heterozygous compound HBB:c.-113A>G heterozygous mutation can aggravate the clinical manifestations ofβ-thalassemia and then show splenomegaly.The discovery of this gene mutation enriches the database of thalassemia gene mutation.At the same time,more comprehensive detection techniques are of great significance for etiological diagnosis,treatment and genetic counseling of clinical patients after routine detection of thalassemia.

关 键 词：Β-地中海贫血 HBB:c.-113A>G杂合 高通量测序 基因突变 

分 类 号：R556[医药卫生—血液循环系统疾病]