Yamsri Supawadee, Prommetta Simaporn, Srivorakun Hataichanok, Taweenan Wachiraporn, Sanchaisuriya Kanokwan, Chaibunruang Attawut, Fucharoen Goonnapa, Fucharoen Supan
Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University Khon Kaen 40002, Thailand.
Am J Transl Res. 2022 Feb 15;14(2):1315-1323. eCollection 2022.
A co-inheritance of α-thalassemia can ameliorate the clinical severity of the hemoglobin (Hb) E-β-thalassemia disease. This information should be provided at prenatal diagnosis. Identification of α-thalassemia in an affected fetus is therefore valuable. We have explored this genetic interaction in a large cohort of affected fetuses with hemoglobin (Hb) E-β-thalassemia in northeast Thailand.
A study was done retrospectively on 1,592 couples at risk of having fetuses with Hb E-β-thalassemia, encountered from January 2011 to December 2019. A total of 415 left-over DNA specimens of the affected fetuses with Hb E-β-thalassemia disease were further investigated. Examination of α-thalassemia was done using gap-PCR or a multiplex PCR assay for simultaneous detection of Hb E and α-thalassemia mutations.
Of the 415 affected fetuses, the two most common β-thalassemia genes found were the codons 41/42 (-TTCT) (199/415; 48.0%) and codon 17 (A-T) (115/415; 27.7%). α-thalassemia was found unexpectedly in 21 (5.1%) fetuses. Hematologic phenotypes of the parents indicated that it was impossible to differentiate a pure β-thalassemia carrier from a double β-thalassemia/α-thalassemia heterozygote unless DNA analysis is performed. In contrast, a reduced level of Hb E in the Hb E carrier (<25%) is a valuable marker for predicting double heterozygosity for Hb E/α-thalassemia. This could be further confirmed using a multiplex PCR assay.
There is a high prevalence of co-inheritance of α-thalassemia in fetuses with Hb E-β-thalassemia disease. In a high-risk population such as Thailand, we recommend screening for α-thalassemia in all affected fetuses with Hb E-β-thalassemia disease and providing complete genetic information to the parents to make appropriate decisions at prenatal diagnosis and genetic counseling.
α地中海贫血的共同遗传可改善血红蛋白E-β地中海贫血疾病的临床严重程度。这一信息应在产前诊断时提供。因此，在受影响胎儿中鉴定α地中海贫血具有重要价值。我们在泰国东北部一大群患有血红蛋白E-β地中海贫血的受影响胎儿中探索了这种基因相互作用。
对2011年1月至2019年12月期间遇到的1592对有患血红蛋白E-β地中海贫血胎儿风险的夫妇进行回顾性研究。对415份患有血红蛋白E-β地中海贫血疾病的受影响胎儿的剩余DNA样本进行了进一步研究。使用缺口PCR或多重PCR检测法检测α地中海贫血，同时检测血红蛋白E和α地中海贫血突变。
在415例受影响胎儿中，发现的两种最常见的β地中海贫血基因是密码子41/42（-TTCT）（199/415；48.）和密码子17（A-T）（115/415；27.7%）。意外地在21例（5.1%）胎儿中发现了α地中海贫血。父母的血液学表型表明，除非进行DNA分析，否则无法区分纯β地中海贫血携带者和双β地中海贫血/α地中海贫血杂合子。相比之下，血红蛋白E携带者中血红蛋白E水平降低（<25%）是预测血红蛋白E/α地中海贫血双杂合性的重要指标。这可以通过多重PCR检测法进一步证实。
血红蛋白E-β地中海贫血疾病胎儿中α地中海贫血共同遗传的患病率很高。在泰国这样的高危人群中，我们建议对所有患有血红蛋白E-β地中海贫血疾病的受影响胎儿进行α地中海贫血筛查，并向父母提供完整的基因信息，以便在产前诊断和遗传咨询时做出适当决策。
