Molecular analysis of alpha- and beta-thalassemia in Meizhou region and comparison of gene mutation spectrum with different regions of southern China

Abstract

Background: Thalassemia is a group of inherited autosomal recessive hemolytic anemia disease caused by reduced or absent synthesis of globin chain/chains of hemoglobin. Only few studies showed the molecular characterization of α- and β-thalassemia in Meizhou city of China. Methods: A total of 22,401 individuals were collected; hematological and hemoglobin electrophoresis analysis and thalassemia genetic testing were performed. Results: Eleven thousand and thirty (49.24%) cases with microcytosis (mean corpuscular volume (MCV) < 82 fl), 11,074 (49.44%) cases with hypochromia (mean corpuscular Hb (MCH) < 27 pg) in 22,401 subjects, 11,085 cases with abnormal hemoglobin results were identified in subjects aged ≥6 months. 7,322 (32.69%) subjects harbored thalassemia mutations, including 4,841 (21.61%) subjects with α-thalassemia, 2,237 (9.99%) with β-thalassemia, and 244 (1.09%) with α-thalassemia combined β-thalassemia. 18 genotypes of α-thalassemia mutations and 27 genotypes of β-thalassemia mutations were characterized. The most frequent α gene mutation was --SEA (64.69%), followed by -α3.7 (19.93%), -α4.2 (7.73%), αCSα (3.97%), and αWSα (2.83%). The six most common β-thalassemia mutations were IVS-II-654 (C>T) (39.79%), CD41-42 (-TCTT) (33.02%), −28 (A>G) (10.38%), CD17 (A>T) (9.08%), CD27-28 (+C) (2.14%), and CD26 (G>A) (2.02%). In addition, MCV and MCH were sensitive markers for α- and β-thalassemia except for -α3.7/αα, -α4.2/αα, αCSα/αα, αWSα/αα, and βCap+40−43/βN. Conclusions: The --SEA, -α3.7, and -α4.2 deletions were the main mutations of α-thalassemia, while IVS-II-654 (C>T), CD41-42 (-TCTT), −28 (A>G), and CD17 (A>T) mutations of β-thalassemia in Meizhou. There were some differences in thalassemia mutation frequencies in Meizhou city from other populations in China.