Genetic determinants of phenotype in beta-thalassemia.
Modifier genes are defined as inherited genetic variation that leads to a qualitative or quantitative difference in disease phenotype. This has made the prediction of the phenotype based upon the genotype more difficult. Beta-thalassemia phenotype is modified by co-existent other genetic alterations. Changes alpha/beta-globin ratio can either ameliorate the disease phenotype or increase the severity of the disease in beta-thalassemia. Primary modifiers primarily affecting the clinical presentation include alpha gene changes, XmnI polymorphism and hereditary persistence of fetal hemoglobin (HPFH) variants. 'Thalassemia intermedia' is a heterogenous group with interplay of several genetic factors. The nature of the beta-genotype as well as the knowledge of the presence or absence of alleviating factors help the physician to decide on commencement of a regular transfusion regime or other lines of management including hydroxyurea therapy. The secondary modifiers affect the severity of jaundice, bone disease, cardiac and thrombotic complications. The present review gives a concise discussion of various modifying genes and the influence on the phenotype of beta-thalassemia.
Panigrahi
Inusha
I
Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh-12, India. inupan@yahoo.com
Agarwal
Sarita
S
D005319:Fetal Hemoglobin / Q000235:genetics; D006801:Humans; D009154:Mutation; D010641:Phenotype; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000235:genetics*
D055544:beta-Globins; D005319:Fetal Hemoglobin