HbH disease results from dysfunction of three, less commonly two, α-globin genes through various combinations of deletion and non-deletion mutations. Characterization of the mutations and the underlying genotypes is fundamental for proper screening and prevention of thalassaemia in any region. The aim of this study was to explore the genetic arrangements of HbH disease and to correlate the genotypes with the clinical phenotypes. A total of 44 HbH disease patients were enrolled in this study. They were clinically and haematologically assessed. The patients were tested for 21 common α-globin gene mutations using multiplex PCR and reverse hybridization. According to the genotype, the patients were categorized into two separate sub-groups, deletion and non-deletion types HbH disease. Within the studied HbH disease patients, eight different α-globin gene mutations were detected in nine different genetic arrangements. The --MED and -α3.7 deletions were the two most frequently encountered mutations (37.5 and 35.2% respectively). Patients with deletion genotypes constituted 70.4%. The most common detected genotype was --MED/−α3.7 (59.1%), followed by αpoly-A1α/αpoly-A1α (13.6%). For the first time, coinheritance of two relatively mild mutations (−α3.7/ααAdana) was unpredictably detected in a 1.5 year-old child with Hb of 7.1 g/dL. The HbH disease patients’ clinical characteristics were variable with no ample difference between the deletion and non-deletion types. These results can be of benefit for the screening and management of thalassaemia in this region.

中文翻译：

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伊拉克北部 HbH 病的基因型-表型相关性

HbH 疾病是由于缺失和非缺失突变的各种组合导致三个（不太常见的两个）α-珠蛋白基因功能障碍所致。突变和潜在基因型的表征对于在任何地区正确筛查和预防地中海贫血至关重要。本研究的目的是探索 HbH 疾病的遗传排列，并将基因型与临床表型相关联。该研究共招募了 44 名 HbH 疾病患者。他们进行了临床和血液学评估。使用多重 PCR 和反向杂交对患者进行了 21 种常见的 α-珠蛋白基因突变检测。根据基因型，将患者分为两个独立的亚组，即缺失型和非缺失型 HbH 疾病。在研究的 HbH 疾病患者中，在九种不同的遗传排列中检测到八种不同的α珠蛋白基因突变。--MED 和 -α3.7 缺失是两个最常见的突变（分别为 37.5 和 35.2%）。具有缺失基因型的患者占70.4%。最常见的检测到的基因型是--MED/-α3.7 (59.1%)，其次是 αpoly-A1α/αpoly-A1α (13.6%)。首次在 Hb 为 7.1 g/dL 的 1.5 岁儿童中意外检测到两个相对温和的突变（-α3.7/ααAdana）的共同遗传。HbH 病患者的临床特征是多变的，缺失型和非缺失型之间没有很大差异。这些结果有助于该地区地中海贫血的筛查和管理。7 个缺失是最常见的两种突变（分别为 37.5% 和 35.2%）。具有缺失基因型的患者占70.4%。最常见的检测到的基因型是--MED/-α3.7 (59.1%)，其次是 αpoly-A1α/αpoly-A1α (13.6%)。首次在 Hb 为 7.1 g/dL 的 1.5 岁儿童中意外检测到两个相对温和的突变（-α3.7/ααAdana）的共同遗传。HbH 病患者的临床特征是多变的，缺失型和非缺失型之间没有很大差异。这些结果有助于该地区地中海贫血的筛查和管理。7 个缺失是最常见的两种突变（分别为 37.5% 和 35.2%）。具有缺失基因型的患者占70.4%。最常见的检测到的基因型是--MED/-α3.7 (59.1%)，其次是 αpoly-A1α/αpoly-A1α (13.6%)。首次在 Hb 为 7.1 g/dL 的 1.5 岁儿童中意外检测到两个相对温和的突变（-α3.7/ααAdana）的共同遗传。HbH 病患者的临床特征是多变的，缺失型和非缺失型之间没有很大差异。这些结果有助于该地区地中海贫血的筛查和管理。首次在 Hb 为 7.1 g/dL 的 1.5 岁儿童中意外检测到两个相对温和的突变（-α3.7/ααAdana）的共同遗传。HbH 病患者的临床特征是多变的，缺失型和非缺失型之间没有很大差异。这些结果有助于该地区地中海贫血的筛查和管理。首次在 Hb 为 7.1 g/dL 的 1.5 岁儿童中意外检测到两个相对温和的突变（-α3.7/ααAdana）的共同遗传。HbH 病患者的临床特征是多变的，缺失型和非缺失型之间没有很大差异。这些结果有助于该地区地中海贫血的筛查和管理。