β地中海贫血患者1 331例出生年份及基因突变类型分析

Genotypic analysis and date-of-birth statistics of 1331 β-thalassemia patients

目的分析广西籍β地中海贫血(以下简称β地贫)患者出生年份及基因突变类型特点,探讨地贫防控政策进一步完善的方向。方法回顾分析2007年1月至2020年12月就诊的资料完整的1331例广西籍重型(TM)β地贫和中间型β地贫(TI)患者的出生年份和基因突变类型特点。结果1331例患者中1987年出生的为10例,此前均为个位数,此后逐年增加,2009年达到顶峰为103例,2010年开始下降,2018年降至18例,2020例降至2例。1331例患者中1293例(97.15%)通过常规基因分析明确基因型,其中β^(0)/β^(0)纯合子344例(26.6%),β^(0)/β^(0)双重杂合子380例(29.4%),β^(0)/β^(+)双重杂合子370例(28.6%),β^(+)/β^(+)纯合子22例(1.7%),β^(+)/β^(+)双重杂合子31例(2.4%),β/HbE 146例(11.3%),有176例(13.6%)患者复合了α地贫。最常见的4种基因型是CD41-42/CD17(205例,15.9%)、CD41-42/CD41-42(197例,15.2%)、CD41-42/-28(96例,7.4%)和CD17/CD17(92例,7.1%)。1331例患者中38例(2.85%)临床诊断TM或TI的患者常规试剂盒只能检出是β地贫杂合子,不能检出完整的基因突变类型,其中26例通过测序明确基因型,检出8种β地贫基因突类型和2种α三联体,出现频率最高的是IVS-Ⅱ-5(10例)和IVS-Ⅰ-2(5例)。结论“广西地贫防治计划”效果显著,未来地贫防控需要重点关注TI和罕见基因突变类型地贫。

Objective To analyze the phenotypic and genetics information of Guangxi-originβ-thalassemia patients and to discuss the optimized strategy towards the prevention of thalassemia.Methods Retrospective study of 1331 Guangxi-originβ-thalassemia(major and intermedia)patients and their birth date with comprehensive data received from our hospital between January 2007 and December 2020.Results The number of patients born in 1987 was 10.The figures before this year was only single digits while they started to increase afterwards.The figure reached the peak of 103 cases in 2009 and started to drop from 2010 and reached the bottom of 2 cases in 2020.Among the 1331 patients,1293(97.15%)were subjected to genetic tests to identify thalassemia mutations.Consequently,we identified 388(26.6%)homozygousβ^(0)/β^(0) patients and 380(29.4%)compound heterozygousβ^(0)/β^(0) patients,370(28.6%)β^(0)/β^(+)patients,22(1.7%)homozygousβ^(+)/β^(+)patients and 31(2.4%)compound heterozygousβ^(+)/β^(+)patients.In addition,we identified 176(13.6%)patients carryingα-thalassemia mutations.The most commonβ-thalassemia genotypes were CD41-42/CD17(205 cases,15.9%),CD41-42/CD41-42(197 cases,15.2%),CD41-42/-28(96 cases,7.4%)and CD17/CD17(92 cases,7.1%).Among the 1331 patients,38 of them(2.85%)can only be detected asβ-thalassemia carriers with routine diagnostic kit.All of these samples were subjected to further sequencing and the genotypes of 26 cases were identified,composed of 8 different rareβ-thalassemia mutations with IVS-Ⅱ-5(13 cases)and IVS-Ⅰ-2(5 cases).Conclusion The effect of Prevention and Treatment of Thalassemia in Guangxi is significant.In the future,we should pay more attention on the prevention of TI patients and identification of rare disease-causing mutations.