Ning Sisi, Qin Yunrong, Xie Yuling, Liang Yunning, Liang Yi, Wei Guanghong, Zhang Yuping, Pan Jinjie, Lu Yinghong, Liang Shiyan, Xu Ruofan, Mao Aiping, Liu Weiwu
Department of Clinical Laboratory, Yulin Women and Children Health Care Hospital, Yulin, Guangxi Zhuang Autonomous Region, China.
Berry Genomics Corporation, Beijing, China.
Hemoglobin. 2024 Nov;48(6):384-388. doi: 10.1080/03630269.2024.2442641. Epub 2024 Dec 18.
In southern China, α-thalassemia is the most prevalent hereditary monogenic disorder, and deletion variants are the predominant form. Conventional thalassemia diagnosis techniques are numerous, however they are all limited in their ability to detect rare deletions. Here, we discuss a family who sought genetic counseling during their fourth pregnancy after experiencing Hb Bart's hydrops fetalis in two of their previous pregnancies. To ascertain the thalassemia genotype, the family members underwent hematological testing, routine genetic analysis and multiplex ligation-dependent probe amplification (MLPA). The precise deletion locations could not be identified, while MLPA detected an unknown copy number variant. Lastly, a rare 11.1 kb deletion located in the gene (Chr16: 170,832-182,004, GRch38/hg38) was directly identified by single-molecule real-time technology (SMRT) sequencing. Furthermore, we confirmed the compound heterozygosity of -- allele and -- allele, which contributed to the explanation of the Hb Bart's hydrops fetalis syndrome in the fetuses from the second and third pregnancies. We have first verified a compound heterozygosity for -- allele and -- allele. This study may provide a reference strategy for the discovery of rare and potentially novel thalassemia variants using a comprehensive method combining SMRT sequencing and conventional diagnostic technology, improving the accuracy and efficacy of thalassemia diagnosis.
在中国南方，α地中海贫血是最常见的遗传性单基因疾病，缺失变异是其主要形式。传统的地中海贫血诊断技术众多，但在检测罕见缺失方面都存在局限性。在此，我们讨论一个家庭，他们在前两胎出现巴氏水肿胎儿后，在第四次怀孕时寻求遗传咨询。为确定地中海贫血基因型，家庭成员接受了血液学检测、常规基因分析和多重连接依赖探针扩增（MLPA）。虽然MLPA检测到一个未知的拷贝数变异，但无法确定精确的缺失位置。最后，通过单分子实时技术（SMRT）测序直接鉴定出位于该基因（Chr16: 170,832-182,004，GRch38/hg38）中的一个罕见的11.1 kb缺失。此外，我们证实了--等位基因和--等位基因的复合杂合性，这有助于解释第二和第三次怀孕胎儿中的巴氏水肿胎儿综合征。我们首次验证了--等位基因和--等位基因的复合杂合性。本研究可能为使用SMRT测序与传统诊断技术相结合的综合方法发现罕见且可能的新型地中海贫血变异提供参考策略，提高地中海贫血诊断的准确性和有效性。
