[The impact and clinical implication of variants in the start codon of HBA gene on the phenotype of thalassemia].

Q4 Medicine

中华医学遗传学杂志 Pub Date : 2025-01-10 DOI:10.3760/cma.j.cn511374-20240829-00461

Bairu Lai, Yiyuan Ge, Xiaomin Ma, Guangkuan Zeng, Xiaohua Yu, Jianlian Liang, Yanbin Cao, Liye Yang

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引用次数: 0

Abstract

Objective: To analyze the correlation between variants in the start codon of the α-globin gene and phenotypes of thalassemia, so as to provide a basis for the diagnosis and prevention of α-thalassemia.

Methods: A retrospective study was conducted on 7 patients diagnosed by Yangjiang People's Hospital and Guangzhou Hybribio Co. Ltd., from June 2019 to October 2022. Routine blood tests and hemoglobin electrophoresis were carried out. Potential variants were identified through polymerase chain reaction (PCR) combined with Reverse dot blotting (RDB), Gap-PCR, and Sanger sequencing. This study has been approved by the Medical Ethics Committee of People's Hospital of Yangjiang (Ethics No: 20240001).

Results: For the 7 patients, results of blood routine test of one case was unknown, and that of another was normal. The remaining 5 cases had presented with microcytic hypochromic anemia. The results of hemoglobin electrophoresis showed that one case had normal Hb A and slightly lower Hb A2, whilst another had significantly decreased Hb A and Hb A2, in addition with the appearance of a Hb H band. The content of Hb Bart's in four neonates was ≥ 0.4%. The remaining one case had no result. Genetic testing has identified 4 rare start codon mutations, namely HBA2: c.2delT, HBA2: c.1A>G, HBA2: c.1A>T, and HBA1: c.2T>C. Among these, Patient 1 had harbored compound heterozygous variants of HBA2: c.427T>C (Hb CS) and HBA2: c.2delT. Patient 4 had harbored compound heterozygous variants of HBA2: c.1A>G and Southeast Asian type deletion.

Conclusion: Heterozygotes with HBA start codon variants usually present as silent or mild thalassemia, and the symptoms of anemia may deteriorate when combined with other α-thalassemia variant. The HBA2: c.1A>T start codon variant was unreported previously in China. The detection of start codon variants has helped to clarify the causes of anemia, genetic counseling, and guidance for reproduction.

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[HBA基因起始密码子变异对地中海贫血表型的影响及临床意义]。

目的：分析α-珠蛋白基因起始密码子变异与地中海贫血表型的相关性，为α-地中海贫血的诊断和预防提供依据。方法：对2019年6月至2022年10月阳江市人民医院和广州海博生物有限公司诊断的7例患者进行回顾性研究。进行常规血液检查和血红蛋白电泳。通过聚合酶链反应（PCR）、反向点印迹（RDB）、Gap-PCR和Sanger测序鉴定潜在变异。本研究已获得阳江市人民医院医学伦理委员会批准（伦理号：20240001）。结果：7例患者中，1例血常规结果不详，1例血常规结果正常。其余5例表现为小细胞性低色素贫血。血红蛋白电泳结果显示，1例患者Hb A正常，Hb A2略低，另1例患者Hb A和Hb A2明显降低，并出现Hb H带。4例新生儿Hb Bart's含量≥0.4%。剩下的一例没有结果。基因检测鉴定出4个罕见的启动密码子突变，分别是HBA2: C. 2delt、HBA2: C. 1a >g、HBA2: C. 1a >T和HBA1: C. 2t >C。其中，患者1携带HBA2: C . 427t >C （Hb CS）和HBA2: C . 2delt的复合杂合变异体。患者4携带HBA2复合杂合变异体：c.1A、>、G和东南亚型缺失。结论：HBA启动密码子变异的杂合子通常表现为沉默或轻度的地中海贫血，与其他α-地中海贫血变异合用时贫血症状可能恶化。HBA2: c.1A >t起始密码子变异此前在中国未见报道。启动密码子变异的检测有助于澄清贫血的原因，遗传咨询和生殖指导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

中华医学遗传学杂志 Medicine-Medicine (all)

CiteScore

0.50

自引率

0.00%

发文量

9521

期刊介绍： Chinese Journal of Medical Genetics is a medical journal, founded in 1984, under the supervision of the China Association for Science and Technology, sponsored by the Chinese Medical Association (hosted by Sichuan University), and is now a monthly magazine, which attaches importance to academic orientation, adheres to the scientific, scholarly, advanced, and innovative, and has a certain degree of influence in the industry. Chinese Journal of Medical Genetics is a journal of Peking University, and is now included in Peking University Journal (Chinese Journal of Humanities and Social Sciences), CSCD Source Journals of Chinese Science Citation Database (with extended version), Statistical Source Journals (China Science and Technology Dissertation Outstanding Journals), Zhi.com (in Chinese), Wipu (in Chinese), Wanfang (in Chinese), CA Chemical Abstracts (U.S.), JST (Japan Science and Technology Science and Technology), and JST (Japan Science and Technology Science and Technology Research Center). ), JST (Japan Science and Technology Agency), Pж (AJ) Abstracts Journal (Russia), Copernicus Index (Poland), Cambridge Scientific Abstracts, Abstracts and Citation Database, Abstracts Magazine, Medical Abstracts, and so on.