Molecular spectrum and carrier frequency of deletional hereditary persistence of fetal hemoglobin and delta-beta thalassemia in Malaysia.

IF 2.8 Q2 HEMATOLOGY
Faidatul Syazlin Abdul Hamid, Sabariah Md Noor, Mei I Lai, Samsol Kamal Mohd Bahari, Ezalia Esa, Ermi Neiza Mohd Sahid, Norafiza Mohd Yasin, Yuslina Mat Yusoff
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引用次数: 0

Abstract

Purpose: Thalassemia is a major public health concern in Southeast Asia, particularly in Malaysia, where a high carrier rate places significant pressure on healthcare systems. Hereditary Persistence of Fetal Hemoglobin (HPFH) and delta-beta (δβ) thalassemia are genetic conditions associated with elevated levels of fetal hemoglobin (Hb F). This study aimed to determine the frequency of common beta (β)-globin gene cluster deletions among Malaysian carriers of HPFH or δβ thalassemia, while also providing an overview of the thalassemia burden in the region.

Methods: A retrospective study was conducted on 534 blood samples submitted to the Institute for Medical Research (IMR), Malaysia, for β-thalassemia genotyping between January 2017 and December 2019. Demographic data, including full blood count parameters and hemoglobin (Hb) analysis, were retrieved. Deoxyribonucleic acid (DNA) was extracted and analyzed using Multiplex Gap-Polymerase Chain Reaction (PCR) to detect large deletions in the β-globin gene cluster.

Results: Seven distinct deletions were identified among the 534 heterozygous carriers. The two most common deletions were Gγ(Aγδβ)°-thalassemia Siriraj I (~ 118 kilobase pairs [kb]) and δβ°-thalassemia Thai (~ 12.5 kb), accounting for 30.0% and 29.8% of cases, respectively. The HPFH-6 deletion was observed in 20.0% of cases, followed by Gγ(Aγδβ)°-thalassemia Asian-Indian Inversion-Deletion (Inv/Del) (14.2%), Gγ(Aγδβ)°-thalassemia Chinese (~ 100 kb) (4.3%), HPFH-3 (0.9%), and Gγ(Aγδβ)°-thalassemia Asian (~ 49.3 kb) (0.7%). The ethnic distribution showed a predominance among Malay patients (93.4%), with specific deletions suggesting ethnic clustering. Genotype-phenotype analysis revealed notable variations in hematological parameters: carriers of HPFH-3 had the highest Hb F levels (25.3 ± 3.1%) as measured by high-performance liquid chromatography (HPLC) and showed the least severe microcytosis, while carriers of δβ°-thalassemia Thai (~ 12.5 kb) demonstrated more pronounced hematological abnormalities. Findings were consistent with previous reports from Southeast Asia, underscoring the importance of incorporating molecular diagnostics into national screening programs. Although Multiplex Gap-PCR is robust, further studies using Next-Generation Sequencing (NGS) and Multiplex Ligation-dependent Probe Amplification (MLPA) are recommended to detect rare or undetected mutations.

Conclusions: This study provides crucial data on the molecular spectrum of HPFH and δβ thalassemia in Malaysia, contributing to improved diagnostic strategies and genetic counselling. Future research should explore additional genetic variants to enhance national thalassemia prevention programs.

马来西亚胎儿血红蛋白和地中海贫血缺失遗传持久性的分子谱和载体频率。
目的:地中海贫血是东南亚的一个主要公共卫生问题,特别是在马来西亚,那里的高带菌率给卫生保健系统带来了巨大压力。遗传性胎儿血红蛋白(HPFH)和δ - β (δβ)地中海贫血是与胎儿血红蛋白(Hb F)水平升高相关的遗传病。本研究旨在确定马来西亚HPFH或δβ地中海贫血携带者中常见β (β)-珠蛋白基因簇缺失的频率,同时也提供了该地区地中海贫血负担的概述。方法:对2017年1月至2019年12月提交给马来西亚医学研究所(IMR)用于β-地中海贫血基因分型的534份血液样本进行回顾性研究。统计数据包括全血细胞计数参数和血红蛋白(Hb)分析。提取脱氧核糖核酸(DNA),采用多重间隙聚合酶链式反应(PCR)检测β-珠蛋白基因簇中的大缺失。结果:在534个杂合携带者中鉴定出7个不同的缺失。最常见的两个缺失是Gγ(a γ γδβ)°-thalassemia Siriraj I(~ 118千碱基对[kb])和δβ°-thalassemia Thai (~ 12.5 kb),分别占30.0%和29.8%。HPFH-6缺失占20.0%,其次是Gγ(Aγδβ)°-地中海贫血亚洲-印度倒置缺失(Inv/Del)(14.2%)、Gγ(Aγδβ)°-地中海贫血中国(~ 100 kb)(4.3%)、HPFH-3(0.9%)和Gγ(Aγδβ)°-地中海贫血亚洲(~ 49.3 kb)(0.7%)。种族分布在马来患者中占优势(93.4%),特异缺失提示种族聚类。基因型-表型分析揭示了血液学参数的显著差异:HPFH-3携带者的Hb F水平最高(25.3±3.1%),表现出最轻微的小细胞增多,而δβ°-thalassemia Thai (~ 12.5 kb)携带者的血液学异常更为明显。研究结果与东南亚以前的报告一致,强调了将分子诊断纳入国家筛查计划的重要性。虽然多重Gap-PCR是可靠的,但建议使用下一代测序(NGS)和多重连接依赖探针扩增(MLPA)进行进一步的研究,以检测罕见或未检测到的突变。结论:本研究提供了马来西亚HPFH和δβ地中海贫血分子谱的重要数据,有助于改进诊断策略和遗传咨询。未来的研究应该探索更多的基因变异,以加强国家地中海贫血预防计划。
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
Blood Research
Blood Research HEMATOLOGY-
CiteScore
3.70
自引率
0.00%
发文量
64
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