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 β-globin gene mutations, α thalassemia, α 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 β-globin gene mutations were identified of which 3.5% were milder mutations. Among the affected fetuses, 29.6% of the β-thalassemia major and 52.9% of the sickle cell anemia (SCA) fetuses had one genetic modifier while 3.7% of the β-thalassemia major and 41.1% of the SCA fetuses had co-inherited two modifiers. α-gene triplication was detected in 16 (3.5%) β-thalassemia/sickle cell heterozygous and normal fetuses of which 5 babies (2 β-thalassemia heterozygous and 3 normal) could be followed up. Of the 2 β-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 β thalassemia major or sickle cell disease were terminated. Parents having heterozygous fetuses with α gene triplication should be followed up periodically after birth for better management of these babies.
Keywords: beta-thalassemia; genetic modifiers; prenetal diagnosis; sickle cell disease.
© 2020 John Wiley & Sons Ltd.