The Correlation of α-Globin Gene Mutations and the XmnI Polymorphism with Clinical Severity of Hb E/β-Thalassemia

Abstract

Clinical severity assessment and molecular analysis of β-, α-globin genes and the −158 (C > T) XmnI polymorphism of the ^Gγ-globin gene were performed in 80 pediatric patients with Hb E (HBB: c.79G > A)/β-thalassemia (β-thal) to investigate the effects of coinheritance of α-thalassemia (α-thal) and other molecular determinants on their clinical severity. The mean age was 9.4 ± 5.1 years. By using clinical severity score, 35 (43.8%), 27 (33.8%) and 18 cases (22.5%) had moderate, mild and severe disease, respectively. Nine β-thal mutations were identified. All were β⁰ or severe β⁺ mutations. Five patients (6.3%) had coinherited α⁰-thal. All five patients had mild disease with baseline hemoglobin (Hb) values of 7.9 ± 1.5 g/dL, mild hepatosplenomegaly and close-to-normal growth. Only one required a red blood cell transfusion. The disease severity was significantly different among the groups with and without α-thal (p = 0.025), but was not different among the groups with or without the XmnI polymorphism (p = 0.071). This study demonstrates that coinheritance of α⁰-thal alleviates the degree of disease severity in Hb E/β-thal. All our patients with coinherited α⁰-thal have mild disease.

• α-Thalassemia (α-thal)
• β-thalassemia (β-thal)
• genotype-phenotype correlation
• Hb E
• northern Thailand
• XmnI polymorphism

Acknowledgements

The authors are grateful to Ms. Arunee Phusua and Ms. Sudjai Suanta at the Thalassemia Laboratory, Ms. Pimnapa Bunturngsook and Ms. Kanlaya Payu at the Hematology Laboratory, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, for their technical assistance.