title: 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.
authors.affiliation: Indian Red Cross Society, Gujarat State Branch, Red Cross Bhavan , Nr. Khadi Board, Ahmedabad , India .
authors.forename: Ashwin P
authors.initials: AP
authors.lastname: Patel
authors.forename: Rupesh B
authors.initials: RB
authors.lastname: Patel
authors.forename: Saumyaa A
authors.initials: SA
authors.lastname: Patel
authors.forename: Salil N
authors.initials: SN
authors.lastname: Vaniawala
authors.forename: Dipika S
authors.initials: DS
authors.lastname: Patel
authors.forename: Naina S
authors.initials: NS
authors.lastname: Shrivastava
authors.forename: Narmadeshwar P
authors.initials: NP
authors.lastname: Sharma
authors.forename: Jayendrasinh V
authors.initials: JV
authors.lastname: Zala
authors.forename: Prakash H
authors.initials: PH
authors.lastname: Parmar
authors.forename: Madhuben R
authors.initials: MR
authors.lastname: Naik
mesh_terms: D000328:Adult; D003062:Codon; D005191:Family Characteristics; D005260:Female; D017353:Gene Deletion; D005820:Genetic Testing; D006801:Humans; D007194:India; D007438:Introns; D008297:Male; D016254:Mutagenesis, Insertional; D009154:Mutation; D017354:Point Mutation; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis; D012923:Social Class; D055544:beta-Globins / Q000737:chemistry / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism
chemical_list: D003062:Codon; D055544:beta-Globins
keywords: DNA mutation analysis; hemoglobinopathy; prenatal diagnosis (PND); red cell indices; thalassemia