Luo Haiyan, Huang Ting, Lu Qing, Zhang Liuyang, Xu Yonghua, Yang Yan, Guo Zhen, Yuan Huizhen, Shen Yinqin, Huang Shuhui, Yang Bicheng, Zou Yongyi, Liu Yanqiu
Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China.
Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China.
Front Genet. 2022 Sep 28;13:992073. doi: 10.3389/fgene.2022.992073. eCollection 2022.
Hemoglobinopathy associated with the gene, with its two general subtypes as thalassemia and abnormal hemoglobin (Hb) variants, is one of the most prevalent hereditary Hb disorders worldwide. Herein we aimed to elucidate the prevalence of -thalassemia and abnormal hemoglobin variants and the prenatal diagnosis of the gene in Jiangxi Province, southern central China. Hematological indices and capillary Hb electrophoresis were conducted for 136,149 subjects who were admitted to Jiangxi Maternal and Child Health Hospital and requested for hemoglobinopathy investigation. Routine α- and -globin genotyping were performed by gap-polymerase chain reaction (Gap-PCR) and reverse dot-blot (RDB) hybridization for the 11,549 individuals suspected to be thalassemia carriers. For participants whose genotypes could not explain their hematological indices, further Sanger sequencing and Gap-PCR were conducted for the detection of rare or novel variants in related globin genes. Prenatal diagnosis was performed for 77 pregnant couples both carrying -thalassemia trait at appropriate gestational ages. Among the 11,549 subjects, 2,548 individuals were identified with -associated hemoglobinopathy based on molecular analysis. A total of 2,358 subjects were identified as -thalassemia heterozygous carriers and nine cases were diagnosed as compound heterozygous -thalassemia. Additionally, 125 cases were detected with composite α- and -thalassemia and the remaining 56 individuals with abnormal Hb variants in the . A total of 35 types of variants were identified in the gene, including 26 types of -thalassemia and nine types of abnormal Hb variants. Four novel variants were firstly reported, including one variant in and three variants in . Overall, 77 prenatal samples underwent -thalassemia molecular diagnosis; 20 fetuses were identified with normal -thalassemia genotypes, 30 fetuses as -thalassemia heterozygotes, 11 as homozygotes, and 16 as compound heterozygotes in . We have demonstrated a relatively high prevalence rate at 1.872% of -hemoglobinopathies including common and rare -thalassemia as well as abnormal Hb variants among large child-bearing population in the Jiangxi area of southern central China for the first time. Our data presents that prenatal diagnosis is an effective way to prevent and control birth defects of -thalassemia.
与该基因相关的血红蛋白病，其两种主要亚型为地中海贫血和异常血红蛋白（Hb）变异体，是全球最常见的遗传性Hb疾病之一。在此，我们旨在阐明中国中南部江西省β地中海贫血和异常血红蛋白变异体的患病率以及该基因的产前诊断情况。对136149名入住江西省妇幼保健院并要求进行血红蛋白病调查的受试者进行了血液学指标检测和毛细血管Hb电泳。对11549名疑似地中海贫血携带者的个体，采用缺口聚合酶链反应（Gap-PCR）和反向点杂交（RDB）杂交技术进行常规α和β珠蛋白基因分型。对于基因型无法解释其血液学指标的参与者，进一步进行桑格测序和Gap-PCR检测相关珠蛋白基因中的罕见或新变异体。对77对在适当孕周均携带β地中海贫血特征的孕妇夫妇进行了产前诊断。在11549名受试者中，基于分子分析确定2548人患有与β相关的血红蛋白病。共鉴定出2358名β地中海贫血杂合子携带者，9例被诊断为复合杂合子β地中海贫血。此外，检测到125例合并α和β地中海贫血，其余56人存在β珠蛋白异常Hb变异体。在β珠蛋白基因中总共鉴定出35种变异体，包括26种β地中海贫血变异体和9种异常Hb变异体。首次报道了4种新变异体，包括β珠蛋白基因中的1种变异体和α珠蛋白基因中的3种变异体。总体而言，77份产前样本接受了β地中海贫血分子诊断；20例胎儿被鉴定为β地中海贫血基因型正常，30例为β地中海贫血杂合子，11例为纯合子，16例为复合杂合子。我们首次证明，在中国中南部江西地区的大量育龄人群中，包括常见和罕见的β地中海贫血以及异常Hb变异体在内的β血红蛋白病患病率相对较高，为1.872%。我们的数据表明，产前诊断是预防和控制β地中海贫血出生缺陷的有效方法。
