Panyasai Sitthichai, Fucharoen Goonnapa, Fucharoen Supan
Biomedical Science Program, Graduate School, Khon Kaen University, Thailand; Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
Clin Chim Acta. 2015 Jan 1;438:226-30. doi: 10.1016/j.cca.2014.09.003. Epub 2014 Sep 8.
We reported molecular and hematological characteristics of δ-globin chain variants and addressed diagnostic consideration of complex hemoglobinopathies caused by their interactions with α- and β-thalassemias.
Study was done on four unrelated Thai subjects with second Hb A2 fractions. Hb analysis was carried out using automated HPLC and capillary electrophoresis. Mutations were identified by DNA analysis. Novel diagnostic methods based on PCR-RFLP and allele specific PCR were developed.
Hb analysis revealed Hb A2 variant in all cases. DNA analysis of δ-globin gene identified the Hb A2-Melbourne [δ43(CD2)Glu→Lys] in combination with α(+)-thalassemia, α(0)-thalassemia and β(0)-thalassemia in the first three cases, respectively. Analysis of the remaining case identified a novel δ-Hb variant namely the Hb A2-Lampang [δ47(CD6)GAT→AAT; Asp→Asn] found in association with Hb E and α(+)-thalassemia. These mutations could be identified using PCR-RFLP and allele specific PCR assays developed.
It is necessary to recognize the Hb A2 variant and to combine the amounts of Hb A2 and Hb A2-variant for a total Hb A2 value to make better diagnostic of these complex syndromes. Co-inheritance of these multiple globin gene defects could lead to complex hemoglobinopathies requiring comprehensive Hb and molecular assessments.
我们报告了δ-珠蛋白链变异体的分子和血液学特征，并探讨了由它们与α-和β-地中海贫血相互作用引起的复杂血红蛋白病的诊断考量。
对4名具有异常Hb A2组分的不相关泰国受试者进行了研究。使用自动高效液相色谱法和毛细管电泳进行血红蛋白分析。通过DNA分析鉴定突变。开发了基于聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和等位基因特异性PCR的新型诊断方法。
血红蛋白分析在所有病例中均显示出Hb A2变异体。对δ-珠蛋白基因的DNA分析在前3例中分别鉴定出与α（+）-地中海贫血、α（0）-地中海贫血和β（0）-地中海贫血相关的Hb A2-墨尔本[δ43（CD2）谷氨酸→赖氨酸]。对其余病例的分析鉴定出一种新型δ-血红蛋白变异体，即与Hb E和α（+）-地中海贫血相关的Hb A2-南邦[δ47（CD6）GAT→AAT；天冬氨酸→天冬酰胺]。使用开发的PCR-RFLP和等位基因特异性PCR检测可以鉴定这些突变。
有必要识别Hb A2变异体，并将Hb A2和Hb A2变异体的量相结合以获得总Hb A2值，以便更好地诊断这些复杂综合征。这些多种珠蛋白基因缺陷的共同遗传可能导致需要全面血红蛋白和分子评估的复杂血红蛋白病。
