β-Thalassemia Mutations in Western India: Outcome of Prenatal Diagnosis in a Hemoglobinopathies Project

Abstract

Prenatal diagnosis (PND) is one of the most cost effective preventive methods, but it is available only in the large cities of India. Therefore, we initiated a program that offers PND and allows us to determine the prevalence of various mutations. Pregnant females (n = 111,426) were screened for hemoglobinopathies using complete blood count (CBC) and high performance liquid chromatography (HPLC). If the female had a hemoglobinopathy, her husband was then tested. If hemoglobinopathies were seen in both partners, a genetic mutation study was performed on the couple. Fetal samples were obtained by either chorionic villus sampling (CVS) in 70.6% or amniocentesis in 29.4%. The study included 282 couples. IVS-I-5 (G > C) was the most common mutation in all castes except in the Sindhis and Lohanas, where the 619 bp deletion was the most common. Prenatal testing was informative in 97.9% of the couples. A significant number of couples (41.0%) underwent PND during their first pregnancy. Seven patients with β-thalassemia (β-thal) trait had normal Hb A₂ levels. The Hb A₂ and Hb F values varied significantly (p < 0.0001 and 0.0082, respectively) among mutations associated with β-thal. The IVS-I-5, 619 bp deletion, codons 41/42 (–CTTT), codons 8/9 (+G) and IVS-I-1 (G > T or G > A), were present in 81.0% of the couples tested. β-Thalassemia mutation frequency varied among the different castes, underlining the need for evolving a testing strategy that considers the caste system. Targeting antenatal clinics could also prove to be a most cost effective way of preventing hemoglobinopathies.

• DNA mutation analysis
• hemoglobinopathy
• prenatal diagnosis (PND)
• red cell indices
• thalassemia

Acknowledgements

We would like to thank Dr. Ishwar C. Verma and his team at the Sir Gangaram Hospital, Delhi, India, for performing mutation analyses and providing technical guidance and Dr. Bharat I. Patel of the Shachi Women’s Hospital, Ahmedabad, India, for obtaining fetal samples for mutation analyses.