Prenatal Diagnosis Center, Quanzhou Women's and Children's Hospital, Quanzhou, Fujian, China.
Department of Ultrasound, Quanzhou Women's and Children's Hospital, Quanzhou, Fujian, China.
Mol Genet Genomic Med. 2024 Jan;12(1):e2365. doi: 10.1002/mgg3.2365.
Rare and novel variants of HBA1/2 and HBB genes resulting in thalassemia and hemoglobin (Hb) variants have been increasingly identified. Our goal was to identify two rare Hb variants in Chinese population using third-generation sequencing (TGS) technology.
Enrolled in this study were two Chinese families from Fujian Province. Hematological screening was conducted using routine blood analysis and Hb capillary electrophoresis analysis. Routine thalassemia gene testing was carried out to detect the common mutations of α- and β-thalassemia in Chinese population. Rare or novel α- and β-globin gene variants were further investigated by TGS.
The proband of family 1 was a female aged 32, with decreased levels of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), Hb A2, and abnormal Hb bands in zone 5 and zone 12. No common thalassemia mutations were detected by routine thalassemia analysis, while a rare α-globin gene variant Hb Jilin [α139(HC1)Lys>Gln (AAA>CAA); HBA2:c.418A>C] was identified by TGS. Subsequent pedigree analysis showed that the proband's son also harbored the Hb Jilin variant with slightly low levels of MCH, Hb A2, and abnormal Hb bands. The proband of family 2 was a male at 41 years of age, exhibiting normal MCV and MCH, but a low level of Hb A2 and an abnormal Hb band in zone 12 without any common α- and β-thalassemia mutations. The subsequent TGS detection demonstrated a rare Hb Beijing [α16(A14)Lys>Asn (AAG>AAT); HBA2:c.51G>T] variant in HBA2 gene.
In this study, for the first time, we present two rare Hb variants of Hb Jilin and Hb Beijing in Fujian Province, Southeast China, using TGS technology.
越来越多的研究发现，HBA1/2 和 HBB 基因的罕见和新型变体可导致地中海贫血和血红蛋白（Hb）变体。我们的目标是使用第三代测序（TGS）技术在中国人群中鉴定两种罕见的 Hb 变体。
本研究纳入了来自福建省的两个中国家庭。使用常规血液分析和 Hb 毛细管电泳分析进行血液学筛查。进行常规地中海贫血基因检测以检测中国人群中常见的 α-和 β-地中海贫血突变。通过 TGS 进一步研究罕见或新型的 α-和 β-珠蛋白基因突变。
家系 1 的先证者为一名 32 岁女性，MCV、MCH、Hb A2 水平降低，区带 5 和区带 12 出现异常 Hb 带。常规地中海贫血分析未检测到常见的地中海贫血突变，而 TGS 鉴定出一种罕见的 α-珠蛋白基因突变 Hb 吉林[α139(HC1)Lys>Gln (AAA>CAA); HBA2:c.418A>C]。随后的家系分析显示，先证者的儿子也携带 Hb 吉林变体，MCH、Hb A2 和异常 Hb 带略低。家系 2 的先证者为 41 岁男性，MCV 和 MCH 正常，但 Hb A2 水平较低，区带 12 出现异常 Hb 带，无常见的 α-和 β-地中海贫血突变。随后的 TGS 检测显示 HBA2 基因中存在罕见的 Hb 北京[α16(A14)Lys>Asn (AAG>AAT); HBA2:c.51G>T]变体。
本研究首次使用 TGS 技术在中国东南沿海福建省发现了 Hb 吉林和 Hb 北京两种罕见的 Hb 变体。
