BACKGROUND Beta (β)-thalassemia is one of the most common inherited disorders worldwide, with high prevalence in the Mediterranean, the Middle East and South Asia. Over the past 40 years, awareness and prevention campaigns in many countries have greatly reduced the incidence of affected child births. In contrast, much remains to be done in South-Asia. Thus, for Pakistan, an estimated ~ 7000 children annually are born with thalassemia, with no sign of improvement. Although there is good agreement that intermarriage of carriers significantly contributes to the high prevalence of the disorder, effective tools for molecular screening and diagnosis on which to base prevention programs are not readily available. METHODS Here, we present results for a novel LeanSequencing™ process to identify a combination of 18 β-thalassemia mutations (including the sickle cell anemia mutation, HbS, and structural variants HbC and HbE) and 2 hemochromatosis mutations in a multi-ethnic population of 274 pediatric and adolescent patients treated at Afzaal Memorial Thalassemia Foundation in Karachi, Pakistan. RESULTS We found substantial differences in the predominance of disease-causing mutations among the principal ethnic groups in our cohort. We also found the hemochromatosis mutation H63D C > G in 61 (or 22.1%) of our patients including 6 (or 2.2%) homozygotes. CONCLUSIONS To our knowledge, this is the first screen combining a large set of β-thalassemia and hemochromatosis mutations, so as to facilitate the early identification of patients who may be at increased potential risk for complications from iron overload and thereby to improve the prospective management of thalassemia patients.

中文翻译：

---

通过可扩展的地中海贫血和血色素沉着病突变分析，实现常规的β地中海贫血预防和患者管理。

背景技术β（β）地中海贫血是全世界最常见的遗传性疾病之一，在地中海，中东和南亚地区患病率很高。在过去的40年中，许多国家的宣传和预防运动大大减少了受影响的儿童出生率。相反，南亚仍有许多工作要做。因此，对于巴基斯坦来说，估计每年约有7000名儿童患有地中海贫血，但没有改善的迹象。尽管人们普遍认为携带者通婚是造成该疾病高发的重要原因，但尚无法获得有效的分子筛查和诊断工具，而这些工具是预防疾病的基础。方法在这里，我们提供了一个新颖的LeanSequencing™方法的结果，该方法可在274个小儿和多民族的多族裔人群中识别出18种β地中海贫血突变（包括镰状细胞贫血突变，HbS以及结构变异HbC和HbE）和2种血色素沉着病突变的组合。巴基斯坦卡拉奇Afzaal纪念地中海贫血基金会接受治疗的青少年患者。结果我们发现该队列主要种族之间的致病突变优势之间存在实质性差异。我们还在61名（或22.1％）患者中发现了血色素沉着病突变H63D C> G，其中包括6名（或2.2％）纯合子。结论据我们所知，这是首次结合大量β地中海贫血和血色素沉着病突变的筛查，