Department of Obstetrics and Gynecology, Xiaolan Hospital Affiliated to Southern Medical University, Zhongshan, Guangdong province, China
Department of Thyroid and Breast, Shanghai Tenth People's Hospital, Shanghai, China.
J Clin Pathol. 2020 Aug;73(8):488-492. doi: 10.1136/jclinpath-2019-206339. Epub 2020 Jan 24.
Thalassaemia is one of the most common genetics disorders in the world, especially in southern China. The aim of the present study was to investigate the feasibility of combining the gap-PCR and next-generation sequencing (NGS) for thalassaemia carrier screening in the Chinese population.
Blood samples were obtained from 944 prepregnancy couples; thalassaemia carrier screening was performed by using a routine haematological method and a combination of gap-PCR and NGS method.
We found that the α thalassaemia carrier rate was 11% (207/1888); the β thalassaemia carrier rate was 3.7% (70/1888); the composite α thalassaemia and β thalassaemia carrier rate was 0.4% (8/1888). We also identified seven novel mutations, including : c.412A>G, -50 (G>A), : c.+129T>A, : c.-64G>C, : c.-180G>C, : c.+5G>A and : c.-113A>G. By comparing the combined gap-PCR and NGS method, the MCV+MCH and HbA2 detection strategy showed a lower sensitivity of 61.05% (105/172) and a higher missed diagnosis ratio of 38.95% (67/172) for α thalassaemia mutations. The sensitivity was improved with the MCV+MCH and HbA2 detection screen when compared with MCV+MCH detection for β thalassaemia (98.51% vs 85.90%).
Our study suggests the combined gap-PCR and NGS method is a cost-effective method for the thalassaemia carrier screening, particularly for the α thalassaemia mutation carriers.
地中海贫血是世界上最常见的遗传性疾病之一，尤其在中国南方。本研究旨在探讨 gap-PCR 和下一代测序（NGS）联合应用于中国人群地中海贫血携带者筛查的可行性。
采集 944 对孕前夫妇的血样；采用常规血液学方法和 gap-PCR 与 NGS 联合方法进行地中海贫血携带者筛查。
我们发现α地中海贫血携带者率为 11%（207/1888）；β地中海贫血携带者率为 3.7%（70/1888）；复合α地中海贫血和β地中海贫血携带者率为 0.4%（8/1888）。我们还鉴定了 7 种新突变，包括 c.412A>G、-50（G>A）、c.+129T>A、c.-64G>C、c.-180G>C、c.+5G>A 和 c.-113A>G。通过比较 gap-PCR 和 NGS 联合方法，MCV+MCH 和 HbA2 检测策略对α地中海贫血突变的敏感性较低，为 61.05%（105/172），漏诊率较高，为 38.95%（67/172）。与 MCV+MCH 检测相比，MCV+MCH 和 HbA2 检测对β地中海贫血的敏感性提高了（98.51% vs 85.90%）。
本研究表明，gap-PCR 和 NGS 联合方法是一种经济有效的地中海贫血携带者筛查方法，尤其适用于α地中海贫血突变携带者。
