Vijay Pratap Singh | PubMed Health

PubMed2005

Spectrum of beta-thalassemia mutations in North Indian states: a beta-thalassemia trait with two mutations in cis.

OBJECTIVES: To study the prevalence of beta-thalassemia mutations in two North Indian states. DESIGN AND METHODS: Mutation(s) were analyzed in 62 patients using 10 sets of allele-specific primers. RESULTS: Four mutations [IVS1 nt5 (G --> C), F.S 8/9 (+G), F.S 41/42 (-TCTT) and del 619 bp] were found to constitute 94.1% of the total alleles studied. Prevalence of IVS1 nt5 (G --> C) was the highest, closely followed by F.S 8/9 (+G). The latter was thus unusually high and not consistent with earlier reports. Two mutations in cis were detected in one carrier of the thalassemia trait and in his father, thus signifying the possibility of vertical transmission of mutations in a single beta-globin allele. CONCLUSIONS: F.S 8/9 (+G), as well as IVS1 nt5 (G --> C), are the major mutations in Indian states; however, the possibility of multiple mutations in cis in a fetus with the thalassemia trait has to be considered in a prenatal screening program.

Alleles↗

PubMed2002

Factor VIII gene polymorphisms in North Indian population: a consensus algorithm for carrier analysis of hemophilia A.

BACKGROUND: Hemophilia A, an X-linked recessive disorder, has the prevalence of 1 male per 7000 of the male population in the Northern states of India. The aim of the present study was to analyze the polymorphisms of the factor VIII gene in a sample population comprised of 22 families (112 persons) in order to formulate an algorithm that would be informative and accurate, yet cost-effective for carrier diagnosis. METHODS: Polymerase chain reaction was used to study the polymorphisms of two intragenic restriction fragment length polymorphic sites (recognized by BclI and HindIII) and an extragenic variable number tandem repeat (VNTR) locus (St14). RESULTS: Fifty-eight percent of the women tested were heterozygous for the BclI restriction fragment length polymorphism (RFLP) (significantly high compared to earlier reports), signifying the usefulness of this marker in carrier detection. About 64% of the families from the target population could be diagnosed using this marker alone. The other intragenic HindIII RFLP site showed a heterozygosity rate of 43% in women, and was effective in diagnosing 50% of the families studied. The population prevalence for '+' alleles of BclI and HindIII were 68% and 33%, respectively. About 88% of the women tested were heterozygous for the St14 locus, and 83% of the families could be diagnosed using this marker alone. The 1390- and 1300-bp alleles were most prevalent, while novel polymorphisms of 1500 and 1345 bp were detected. CONCLUSIONS: Based on the above data, we suggest screening hemophilic families first for BclI polymorphism, followed by an analysis for HindIII polymorphism in case of homozygosity at the BclI site. When both were noninformative, analysis of St14 locus would be necessary.

Algorithms↗