Zhuhai Institute of Medical Genetics, Zhuhai Women and Children's Hospital, Zhuhai, Guangdong, China.
Innovation Center for Diagnostics and Treatment of Thalassemia, Nanfang Hospital, Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Clin Biochem. 2024 Dec;133-134:110832. doi: 10.1016/j.clinbiochem.2024.110832. Epub 2024 Oct 5.
Thalassemia is a prevalent monogenic blood disorder, clinically classified into alpha- and beta-thalassemia, characterized by the imbalance of the alpha- and beta-globin chains that constitute adult hemoglobin. Copy number variations (CNVs) and single nucleotide variants in globin genes are the primary genetic defects causing thalassemia.
During a prenatal examination, a pregnant woman was suspected to be a carrier of thalassemia, exhibiting microcytic hypochromic anemia and abnormal hemoglobin constituents. Gap-polymerase chain reaction (Gap-PCR) and reverse dot blot (PCR-RDB) techniques did not detect any common thalassemia mutations. We conducted hematological examination and further genetic analyses on the proband's family with three generations. Multiplex ligation-dependent probe amplification (MLPA) was employed to identify CNVs, targeted next-generation sequencing was used to screen for potential pathogenic variants, which were subsequently validated by Sanger sequencing. The hematological parameters of the proband, her father and her son all indicated they were beta-thalassemia carriers. MLPA results revealed a large deletion in beta-globin cluster. Further investigation confirmed the presence of a novel 8.2 kb deletion (NC_000011.10:g.5224208_5232469del) in the proband, her father, and her son, specifically covering the entire HBB gene while not impacting other globin genes.
We found a novel 8.2 kb deletion leading to beta-thalassemia in a Chinese family in which three generations had been affected. This novel deletion may broaden the spectrum of known mutations in thalassemia and provide a reference for clinically suspected cases.
地中海贫血是一种常见的单基因血液疾病，临床上分为α-和β-地中海贫血，其特征是构成成人血红蛋白的α-和β-珠蛋白链失衡。珠蛋白基因中的拷贝数变异（CNVs）和单核苷酸变异是导致地中海贫血的主要遗传缺陷。
在产前检查中，一名孕妇被怀疑为地中海贫血携带者，表现为小细胞低色素性贫血和异常血红蛋白成分。Gap-聚合酶链反应（Gap-PCR）和反向点印迹（PCR-RDB）技术未检测到任何常见的地中海贫血突变。我们对先证者的三代家系进行了血液学检查和进一步的遗传学分析。多重连接依赖性探针扩增（MLPA）用于识别 CNVs，靶向下一代测序用于筛选潜在的致病性变异，随后通过 Sanger 测序进行验证。先证者、其父亲和儿子的血液学参数均表明他们是β-地中海贫血携带者。MLPA 结果显示β-珠蛋白簇存在大片段缺失。进一步的研究证实，先证者、其父亲和儿子均存在一个新的 8.2kb 缺失（NC_000011.10：g.5224208_5232469del），该缺失覆盖了整个 HBB 基因，但不影响其他珠蛋白基因。
我们发现了一个新的 8.2kb 缺失，导致一个中国家庭三代人都患有β-地中海贫血。该新缺失可能拓宽了地中海贫血已知突变谱，并为临床疑似病例提供了参考。
