title: 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 (G)γ-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.
authors.affiliation: Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University , Chiang Mai , Thailand.
authors.forename: Pimlak
authors.initials: P
authors.lastname: Charoenkwan
authors.forename: Pimjan
authors.initials: P
authors.lastname: Teerachaimahit
authors.forename: Torpong
authors.initials: T
authors.lastname: Sanguansermsri
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003062:Codon; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D006446:Hemoglobin E / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007438:Introns; D008297:Male; D009154:Mutation; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012189:Retrospective Studies; D017384:Sequence Deletion; D012720:Severity of Illness Index; D013785:Thailand; D055542:alpha-Globins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D017085:alpha-Thalassemia / Q000097:blood / Q000150:complications / Q000235:genetics*; D017086:beta-Thalassemia / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D055545:gamma-Globins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
chemical_list: D003062:Codon; D055542:alpha-Globins; D055545:gamma-Globins; D006446:Hemoglobin E; C028649:endodeoxyribonuclease XmnI; D015252:Deoxyribonucleases, Type II Site-Specific
keywords: Hb E; XmnI polymorphism; genotype-phenotype correlation; northern Thailand; α-Thalassemia (α-thal); β-thalassemia (β-thal)