Tan Linglong, Huang Ting, Luo Laipeng, Ma Pengpeng, Liu Jia, Zou Jun, Lu Qing, Zou Yongyi, Liu Yanqiu, Luo Haiyan, Yang Bicheng
The Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, China.
The Department of Laboratory Medicine, Jiangxi Maternal and Child Health Hospital, Nanchang, China.
Hemoglobin. 2024 Nov;48(6):369-374. doi: 10.1080/03630269.2024.2438707. Epub 2024 Dec 10.
Hemoglobin disorders are highly prevalent inherited hematological defects in Southern China. The identification of novel variants in globin genes and accurate assessment of hematological parameters play a crucial role in precise genetic counseling and clinical practice. Peripheral blood samples were collected for hematological analysis, including red blood cell and hemoglobin assessment, while serum ferritin levels were measured to detect iron depletion. Thalassemia carrier identification was conducted in four subjects admitted to Jiangxi Maternal and Child Health Hospital using next-generation sequencing and Gap-PCR due to the high prevalence of thalassemia in Jiangxi Province. The identified rare or novel small nucleotide variants were subsequently validated through Sanger sequencing. A total of four novel variants were identified incidentally in four unrelated subjects, including : c.300G > C (p.Lys100Asn): c.212T > A (p.Val71Glu), : c.28T > A (p.Ser10Thr) and c.167T > C (p.Met56Thr). The proband carrying the c.212T > A and c.300G > C variants exhibited normal hematological findings, while capillary electrophoresis revealed the presence of abnormal hemoglobin fractions at 22.4% and 10.9%. The subjects with variant : c.28T > A and c.167T > C all demonstrated normal hematological findings and normal hemoglobin fraction as determined by capillary electrophoresis or ion exchange high-resolution liquid chromatography (HPLC). The two variants exhibiting abnormal fractions of hemoglobin were designated as Hb Jiangxi (: c.212T > A) and Hb Fulton (: c.300G > C). Meanwhile, : c.28T > A and : c.167T > C were referred to as Hb Yichun and Hb Jinxian, respectively. We here reported four novel variants in globin genes and their hematological findings in for unrelated Chinese individuals in Southern China. Our research has expanded the existing genetic spectrum of globin genes and enhanced our understanding of the hematological profiles associated with variant hemoglobin.
血红蛋白疾病是中国南方高度流行的遗传性血液学缺陷。鉴定珠蛋白基因中的新变异以及准确评估血液学参数在精准遗传咨询和临床实践中起着至关重要的作用。采集外周血样本进行血液学分析，包括红细胞和血红蛋白评估，同时测量血清铁蛋白水平以检测铁缺乏。由于江西省地中海贫血患病率高，对江西省妇幼保健院收治的4名患者采用下一代测序和缺口聚合酶链反应（Gap-PCR）进行地中海贫血携带者鉴定。随后通过桑格测序验证鉴定出的罕见或新的小核苷酸变异。在4名无亲缘关系的受试者中偶然共鉴定出4个新变异，包括：c.300G＞C（p.Lys100Asn）、c.212T＞A（p.Val71Glu）、c.28T＞A（p.Ser10Thr）和c.167T＞C（p.Met56Thr）。携带c.212T＞A和c.300G＞C变异的先证者血液学检查结果正常，而毛细管电泳显示异常血红蛋白组分占比分别为22.4%和10.9%。携带c.28T＞A和c.167T＞C变异的受试者血液学检查结果均正常，毛细管电泳或离子交换高分辨率液相色谱（HPLC）测定的血红蛋白组分也正常。表现出异常血红蛋白组分的两个变异分别命名为Hb江西（c.212T＞A）和Hb富尔顿（c.300G＞C）。同时，c.28T＞A和c.167T＞C分别称为Hb宜春和Hb进贤。我们在此报告了中国南方4名无亲缘关系个体中珠蛋白基因的4个新变异及其血液学检查结果。我们的研究扩展了现有的珠蛋白基因遗传谱，加深了我们对与变异血红蛋白相关血液学特征的理解。
