Prenatal diagnosis of haemoglobinopathies

Abstract

Background. Haemoglobinopathies constitute a major health problem in the Indian subcontinent. In the absence of any method for achieving complete cure and treatment being expensive, prenatal diagnosis and selective termination of an affected foetus is a feasible option to decrease the disease load. We report our experience with prenatal diagnosis of haemoglobinopathies over a two-and-a-half year period in 257 pregnancies. Methods. Amplification refractory mutation system (ARMS) was used to detect β-thalassaemia, haemoglobin E and sickle cell mutations. Results. Five mutations in the β-globin gene which are common in the Indian population were detected in 92.3% of mutant chromosomes, whereas 3.1% of chromosomes carried rare mutations followed by 0.8% haemoglobin E and 0.4% sickle cell mutations. Mutations in 3.3% chromosomes were uncharacterized. The prenatal procedure, carried out early in pregnancy, was a chorionic villus sampling in most cases. A confirmed diagnosis based on ARMS-PCR was given in 241 (93.8%) cases. In 10 cases (3.9%) linkage analysis was required to confirm the foetal status, as mutations in both parents were not identified or the chorionic villus sample carried the single identified mutation. Four families with haemoglobin E-β thalassaemia and one family with sickle cell disease were also included. Of the study population, 91.25% of the couples had a previous child with haemoglobinopathy, whereas 8.75% of the couples came before the birth of the first affected child. Conclusion. We conclude that ARMS-PCR is a highly sensitive technique for detecting mutations in the β-globin gene and its efficacy in the prenatal diagnosis of haemoglobinopathies is proven.