目的 探讨中国广东人群δ珠蛋白（HBD）基因变异谱及δ地中海贫血血液学表型特征。 方法 采用回顾性病例分析研究，收集2020年7月至2022年12月参加广州市免费地中海贫血筛查的11 616对夫妇血液样本，进行血常规和血红蛋白（Hb）毛细管电泳分析，依据以上结果，共154例样本入组研究：（1）HbA2<2.0%且无HbF条带组35例；（2）HbA2<2.0%伴HbF条带组64例；（3）HbA2<2.0%伴可疑HbA2变异体组25例；（4）2.0%≤HbA2<3.5%伴HbF条带且血常规异常［红细胞平均体积（MCV）<82 fl和/或红细胞平均血红蛋白含量（MCH）<27 pg］组25例；（5）2.0%≤HbA2<3.0%伴β地中海贫血基因携带组5例。采用Sanger 测序检测δ珠蛋白基因的单核苷酸变异。 结果 （1）共检出22种HBD基因变异，包括6种新变异，前3位基因变异分别为c.-127T>C（57.02%，65/114）、c.-80T>C（9.65%，11/114）与c.349C>T（7.89%，9/114）。（2）HbA2<2.0%且无HbF条带组检出HBD基因变异22例（62.85%，22/35），其中7例MCV、MCH均低于正常参考值，4例合并α地中海贫血；13例未检出HBD基因变异，其中12例MCV、MCH均明显低于正常参考值。19例血常规异常样本中，HBD基因变异检出异常者（7例）HbA2水平低于未检出者（12例）（P<0.01）。（3）HbA2<2.0%伴HbF条带组检出HBD基因变异59例（92.18%，59/64），均为启动子区变异，59例样本HbF均<5.0%；5例HbF>5.0%样本均未检出HBD基因变异。（4）HbA2<2.0%伴可疑HbA2变异体组HBD基因变异检出率为100%（25/25），δ珠蛋白变异体值<1.0%。（5）2.0%≤HbA2<3.5%伴HbF条带且血常规异常组未检出HBD基因变异。（6）2.0%≤HbA2<3.0%伴β地中海贫血基因携带组5例全部检出HBD基因变异，HbA2值为（2.62±0.17）%，HbF值（3.62±2.22）%。 结论 HBD基因变异类型多样，c.-127T>C是中国广东人群最常见类型；启动子区突变可导致HbA2降低，HbF升高，但HbF值通常<5.0%，合并β地中海贫血可能>5.0%。本研究丰富了广东人群HBD基因突变谱。 Objective To investigate genetic variation profiles of δ-globin (HBD gene) and hematological phenotypes in Guangdong population. Methods Retrospective case analysis was performed in this study. Blood samples of 11 616 couples who participated in free thalassemia screening in Guangzhou from July 2020 to December 2022 were collected which underwent blood routine tests and hemoglobin (Hb) capillary electrophoresis. According to the results, 154 samples were enrolled in this study: (1)group of 35 cases with HbA2 <2.0% but no HbF band (2)group of 64 cases with HbA 2 < 2.0% and HbF band (3)group of 25 cases with HbA 2 <2.0% and suspected HbA 2 variants (4) group of 25 cases with HbA2 ≥2.0% and <3.5% and HbF band, as well as abnormal blood routine report [mean corpuscular volume (MCV) <82 fl and/or mean corpuscular hemoglobin (MCH) <27 pg] (5)group of 5 cases with HbA 2 ≥2.0% and <3.0% accompanied with β thalassemia gene carriers Sanger sequencing was used to detect single nucleotide variants of δ-globin. Results (1) A total of 22 genetic variations were detected, including 6 de novo variations, and the top 3 genetic variations were respectively c.-127T>C (57.02%, 65/114), c.-80T>C (9.65%, 11/114), c.349C>T (7.89%, 9/114). (2) In group of patients with HbA2 <2.0% but no HbF band, 22 cases (62.85%, 22/35) had HBD gene variation, including 7 cases with MCV and MCH lower than reference values, 4 cases with α thalassemia 13 cases had no HBD gene variation, including 12 cases with lower MCV and MCH. Among 19 cases with abnormal blood routine test results, levels of HbA 2 in patients (7 cases) with HBD gene variation were lower compared with those without HBD gene variation (12 cases) (P<0.01%). (3)In group of patients with HbA2<2.0% with HbF band, 59 cases (92.18%, 59/64) had HBD gene variations whose mutations all occurred in promoter region, and the HbF were all lower than 5.0% 5 cases with HbF >5.0% had no HBD gene variation. (4) In group of patients with HbA2 <2.0% and suspected HbA 2 variants, the detection rate was 100% (25/25) and δ-globin variants <1.0%. (5) In group of patients with HbA 2 ≥2.0% and <3.5% and HbF band accompanied with abnormal blood routine results, no HBD gene variation was found. (6) In group of 5 patients with HbA 2 ≥2.0% and <3.0% with β thalassemia gene carriers, HBD gene variation were found in all cases, and the level of HbA 2 was (2.62±0.17)% and HbF was (3.62±2.22)%. Conclusions There are various genotypes of HBD gene variation, among which HBD: c.-127T>C is the most common in Guangdong population in China. Mutations in the promoter region may cause decrease in HbA2 and increase in HbF which is mostly less than 5% but exceeds 5.0% when combined with β thalassemia. Our study enriched the gene mutation profiles of HBD gene in Guangdong population.
Study of genetic profiles and haematological phenotypes of δ-thalassemia in Guangdong population
Objective To investigate genetic variation profiles of δ-globin (HBD gene) and hematological phenotypes in Guangdong population. Methods Retrospective case analysis was performed in this study. Blood samples of 11 616 couples who participated in free thalassemia screening in Guangzhou from July 2020 to December 2022 were collected which underwent blood routine tests and hemoglobin (Hb) capillary electrophoresis. According to the results, 154 samples were enrolled in this study: (1)group of 35 cases with HbA2 <2.0% but no HbF band (2)group of 64 cases with HbA 2 < 2.0% and HbF band (3)group of 25 cases with HbA 2 <2.0% and suspected HbA 2 variants (4) group of 25 cases with HbA2 ≥2.0% and <3.5% and HbF band, as well as abnormal blood routine report [mean corpuscular volume (MCV) <82 fl and/or mean corpuscular hemoglobin (MCH) <27 pg] (5)group of 5 cases with HbA 2 ≥2.0% and <3.0% accompanied with β thalassemia gene carriers Sanger sequencing was used to detect single nucleotide variants of δ-globin. Results (1) A total of 22 genetic variations were detected, including 6 de novo variations, and the top 3 genetic variations were respectively c.-127T>C (57.02%, 65/114), c.-80T>C (9.65%, 11/114), c.349C>T (7.89%, 9/114). (2) In group of patients with HbA2 <2.0% but no HbF band, 22 cases (62.85%, 22/35) had HBD gene variation, including 7 cases with MCV and MCH lower than reference values, 4 cases with α thalassemia 13 cases had no HBD gene variation, including 12 cases with lower MCV and MCH. Among 19 cases with abnormal blood routine test results, levels of HbA 2 in patients (7 cases) with HBD gene variation were lower compared with those without HBD gene variation (12 cases) (P<0.01%). (3)In group of patients with HbA2<2.0% with HbF band, 59 cases (92.18%, 59/64) had HBD gene variations whose mutations all occurred in promoter region, and the HbF were all lower than 5.0% 5 cases with HbF >5.0% had no HBD gene variation. (4) In group of patients with HbA2 <2.0% and suspected HbA 2 variants, the detection rate was 100% (25/25) and δ-globin variants <1.0%. (5) In group of patients with HbA 2 ≥2.0% and <3.5% and HbF band accompanied with abnormal blood routine results, no HBD gene variation was found. (6) In group of 5 patients with HbA 2 ≥2.0% and <3.0% with β thalassemia gene carriers, HBD gene variation were found in all cases, and the level of HbA 2 was (2.62±0.17)% and HbF was (3.62±2.22)%. Conclusions There are various genotypes of HBD gene variation, among which HBD: c.-127T>C is the most common in Guangdong population in China. Mutations in the promoter region may cause decrease in HbA2 and increase in HbF which is mostly less than 5% but exceeds 5.0% when combined with β thalassemia. Our study enriched the gene mutation profiles of HBD gene in Guangdong population.
万方数据
