An interplay of alleviating mutations in the clinical phenotype of beta-thalassaemia intermedia

Abstract

Prediction of a beta-thalassaemia major phenotype from the beta-genotype is generally relatively straightforward. However, despite the ability to accurately define the beta-thalassaemia mutations, prediction of a beta-thalassaemia intermedia phenotype from the genotype sometimes remains problematic and this has important implications in genetic counselling and prenatal diagnosis. We report a 11-year-old Indian male child with a thalassaemia intermedia phenotype. beta-Globin gene analysis of the family showed that he was a compound heterozygote with the -88 (C-->T) beta+-mutation and the IVS1 nt 130 (G-->C) beta0-mutation. Both these mutations are rare among Indians. The propositus was also found to be heterozygous for the XmnI polymorphism and had a normal alpha-genotype. In this family interplay of two alleviating mutations (a milder promoter mutation along with a gene for raised HbF) might have synergistically compensated for lack of globin chains in the patient. Hence, the nature of the beta-genotype as well as the knowledge of the presence or absence of alleviating factors will help the clinician to decide whether early commencement of a regular transfusion regime is necessary.

Identification of Two Rare β-Globin Gene Mutations in a Patient with β-Thalassemia Intermedia from Azerbaijan

“…This may result from inheritance of a β þ -thal mutations resulting in a residual β-globin chain output or reduction of α-globin chain synthesis because of coinheritance of α-thal or genetic interaction, which results in increased synthesis of fetal Hb (2). Interplay of these alleviating or ameliorating factors plays an important role in assessing the clinical phenotype of the patients (3). Accurate and precise prediction of phenotype from genotype has an important implication for prenatal diagnosis.…”