Abstract

Interaction of structural hemoglobin (Hb) variants with α- or β-globin defects are occasional in Southeast Asia. Herein we provide the first description of Hb Athens-Georgia (Hb A-Ga) in association with deletional Hb H disease, a novel combination previously undescribed in the population. Hematological, Hb and DNA analysis, and β-globin haplotype analyses were performed in seven participants from one ethnic Thai family. Hemoglobin analysis by capillary electrophoresis revealed an abnormal Hb fraction in the proband, his father and grandmother (I-2). DNA sequencing revealed that the G > A substitution at codon 40 of the β-globin gene was identical to the Hb A-Ga (HBB:c.122G > A). Interestingly, α-thal-1 (SEA deletion) and α-thal-2 (-α^3.7 deletion) were identified in the proband resulting in Hb H disease, while α-thal-1 was identified in the father, and no α-thal was observed in I-2. Hematological analysis indicated that the proband (β^A-Ga/β^A, –^SEA/-α^3.7) had moderate anemia and was markedly hypochromic with microcytic red blood cells (RBCs). The father (β^A-Ga/β^A, –^SEA/αα) presented mild microcytic anemia, while normal hematology was observed in the I-2 who was heterozygous for Hb Athens-Georgia (β^A-Ga/β^A, αα/αα). The relative level of Hb A-Ga was distinctly reduced according to the degree of α-globin defects. The developed allele-specific PCR method can successfully be used for confirmation of Hb A-Ga. The Thai Hb A-Ga allele associated with a β-haplotype [+ - - - - - +]. These findings were in accordance with the previous conclusion that this variant is a non-pathological β-Hb variant.

摘要

结构性血红蛋白 (Hb) 变体与 α 或 β 珠蛋白缺陷的相互作用在东南亚偶尔会发生。在此，我们首次描述了 Hb 雅典-乔治亚 (Hb A-Ga) 与缺失性 Hb H 疾病相关的情况，这是一种以前未在人群中描述过的新组合。对来自一个泰族家庭的 7 名参与者进行了血液学、Hb 和 DNA 分析以及 β-珠蛋白单倍型分析。毛细管电泳的血红蛋白分析显示先证者、他的父亲和祖母的 Hb 分数异常 (I-2)。DNA 测序显示，β-珠蛋白基因第 40 位密码子的 G > A 取代与 Hb A-Ga 相同（HBB :c.122G > A）。有趣的是，α-thal-1（SEA 缺失）和 α-thal-2（-α ^3.7缺失）在导致 Hb H 病的先证者中被鉴定，而在父亲中鉴定出 α-thal-1，而在 I-2 中没有观察到 α-thal。血液学分析表明先证者 (β ^A-Ga /β ^A , – ^SEA /-α ^3.7 ) 有中度贫血，小红细胞 (RBC) 显着低色素。父亲 (β ^A-Ga /β ^A , – ^SEA /αα) 出现轻度小细胞性贫血，而在 I-2 中观察到正常的血液学，I-2 是 Hb 雅典-乔治亚 (β ^A-Ga /β ^A ) 杂合子, αα/αα)。根据α-珠蛋白缺陷的程度，Hb A-Ga 的相对水平明显降低。开发的等位基因特异性 PCR 方法可成功用于 Hb A-Ga 的确认。Thai Hb A-Ga 等位基因与 β 单倍型 [+ - - - - - +] 相关。这些发现与之前的结论一致，即该变体是一种非病理性 β-Hb 变体。