*Department of Haematology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Nedlands †School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands ‡School of Biomedical Sciences, Curtin University, Bentley, Western Australia, Australia.
Pathology. 2013 Oct;45(6):591-4. doi: 10.1097/PAT.0b013e32836526d7.
Alpha (α) thalassaemia may be caused by large deletions of the α globin gene(s), or rarely, non-deletional mutations. Both types of mutations may co-exist, and if located on the same allele (α), produce a reproductive risk of hydrops fetalis. We illustrate how clinical-laboratory correlation and accurate α gene sequencing are essential in identifying such patients.
Nine asymptomatic patients with -α thalassaemia trait were noted to have significant microcytosis that was insufficiently explained by a single α deletion. Hence α1 and α2 globin gene sequencing were performed, which detected a non-deletional mutation in all patients. A new set of α1 specific primers were designed for separate sequencing of the α1 gene and the -α fusion gene, respectively, so that the non-deletional mutation could be localised to the correct allele.
In six of nine patients tested, the non-deletional mutation was on the α1 globin gene. In three patients the mutation was located on the -α fusion gene. The latter group functionally has an α allele (αα/-) with a reproductive risk for Hb Barts hydrops fetalis.
Non-deletional mutations can occur on the α globin gene or a fusion gene such as the -α allele. Identification and accurate localisation of these mutations is important as this can have significant reproductive implications.
α 地中海贫血可能由α 珠蛋白基因（s）的大片段缺失引起，或罕见地，由非缺失性突变引起。这两种类型的突变可能共存，如果位于同一等位基因（α）上，会产生胎儿水肿的生殖风险。我们举例说明了临床-实验室相关性和准确的α 基因测序在识别此类患者中的重要性。
注意到 9 名无症状的 -α 地中海贫血特征患者存在明显的小细胞性贫血，这不能仅用单个α 缺失来解释。因此，进行了α1 和α2 珠蛋白基因测序，在所有患者中均检测到非缺失性突变。设计了一组新的α1 特异性引物，用于分别对α1 基因和 -α 融合基因进行测序，以便将非缺失性突变定位到正确的等位基因上。
在 9 名受检患者中的 6 名中，非缺失性突变位于α1 珠蛋白基因上。在 3 名患者中，突变位于 -α 融合基因上。后者在功能上具有α 等位基因（αα/-），存在 Hb Barts 胎儿水肿的生殖风险。
非缺失性突变可以发生在α 珠蛋白基因或 -α 等位基因等融合基因上。识别和准确定位这些突变很重要，因为这可能具有重要的生殖意义。
