Prevalence of globin gene modifiers encountered in fetuses during antenatal diagnosis of hemoglobinopathies

Abstract

Introduction The hemoglobinopathies are the commonest group of single gene disorders in the Indian subcontinent. Although genetic modifiers are known to have a remarkable effect on phenotypic expression, the effects of the possible co-inheritance of different modifiers are not taken into account during prenatal diagnosis. The present study was undertaken to look for the frequency of globin gene modifiers like the types of beta-globin gene mutations, alpha thalassemia, alpha gene triplication, and the Xmn1 polymorphism in fetuses during antenatal diagnosis of hemoglobinopathies. Materials and methods A total of 580 fetuses with different diagnoses were screened for the presence of genetic modifiers. Results Twenty-two different beta-globin gene mutations were identified of which 3.5% were milder mutations. Among the affected fetuses, 29.6% of the beta-thalassemia major and 52.9% of the sickle cell anemia (SCA) fetuses had one genetic modifier while 3.7% of the beta-thalassemia major and 41.1% of the SCA fetuses had co-inherited two modifiers. alpha-gene triplication was detected in 16 (3.5%) beta-thalassemia/sickle cell heterozygous and normal fetuses of which 5 babies (2 beta-thalassemia heterozygous and 3 normal) could be followed up. Of the 2 beta-thalassemia heterozygous babies, one had a severe clinical presentation. Conclusion Many fetuses had one or two gene modifiers. However, the impact of these on ameliorating the severity of the disease could not be evaluated as all the fetuses with beta thalassemia major or sickle cell disease were terminated. Parents having heterozygous fetuses with alpha gene triplication should be followed up periodically after birth for better management of these babies.