Molecular genetics and prenatal diagnosis of beta thalassemia to control transfusion dependent births in carrier Pakistani couples.

OBJECTIVE To examine molecular genetics and prenatal diagnosis of beta-thalassaemia. METHODS The study was conducted at the COMSATS Institute of Information Technology, Sahiwal, Pakistan, from October 2012 to October 2013, and comprised families having children affected by thalassaemia and autosomal recessive b-thalassemia. Blood samples of thalassaemic children and their parents were collected from different areas of Pakistan. They were screened for reported mutations through amplification refractory mutation system-polymerase chain reaction. Once mutation was characterised, chorionicvilus sampling was carried out to provide the retrospective first trimester prenatal diagnosis. RESULTS A total of five families were included in this study. Electropherogram showed that both mother and father were heterozygous (carrier) for intervening sequence I-5 mutation whereas the affected child was homozygous for this mutation. Five chorionic villus samples were examined to analyse the molecular defects which were responsible for beta-thalassaemia in the families. Prenatal diagnosis was performed for these families. They had at least one affected child (thalassaemia major) who was transfusion-dependant. Amplification refractory mutation system-polymerase chain reaction was found to be a very sensitive method to find the known point mutations present in beta-globin gene. Point mutations identified included intervening sequence I-5 (G-C), frameshift codon8/9 (+G) and frameshift codon-41/42 (-TTCT). CONCLUSIONS It is the best preventive action to adopt the screening process to overcome the disease.