Genetic Heterogeneity of Beta Globin Mutations Among Asian-Indians and Importance in Genetic Counselling and Diagnosis

Abstract

There are an estimated 45 million carriers of β-thalassemia trait and about 12,000–15,000 infants with β-thalassemia major are born every year in India. Thalassemia major constitutes a significant burden on the health care system. The burden of thalassemia major can be decreased by premarital screening and prenatal diagnosis. The success of prenatal diagnosis requires proper knowledge of spectrum of β-thalassemia mutations. In present study, β-thalassemia mutations were characterized in 300 thalassemia cases from 2007 to 2010 using ARMS-PCR and DNA sequencing. The five most common mutations accounted 78.9% of the studied chromosomes that includes IVS1-5(G>C), Cod 41-42(-TCTT), Cod8-9(+G), Cod16(−C) and 619bp del. Though IVS1-5(G>C) is most common mutation in all the communities, the percentage prevalence were calculated on sub caste basis and found that IVS1-5(G>C) percentage prevalence varied from 25 to 60 in Aroras & Khatris and Thakur respectively. Interestingly Cod41-42(−TCTT) mutation which is the second commonest among the mutations reported was totally absent in Kayasthas and Muslim community. These findings have implications for providing molecular diagnosis, genetic counseling and prenatal diagnosis to high risk couples of β-thalassemia.

Profile of Anemia with special reference to hemoglobinopathies in a tertiary care centre in Madhya Pradesh

“…The inherited disorders of hemoglobin, particularly the βthalassemia and their interaction with hemoglobin S (HbS) are a considerable health problem in India and contribute significantly to morbidity and mortality. Earlier studies have shown that the overall prevalence of β-thalassemia is 3-4 % with an estimate of around 8,000 to 10,000 new births with major disease each year [23,24].…”

The phenotypic and molecular diversity of hemoglobinopathies in India: A review of 15 years at a referral center

“…IVS I‐5 (G>C) has remained the predominant mutation in all these studies with regional variations in frequencies of the other common mutations. The distribution of mutations reported from different states in India has been collated in a few studies . A meta‐analysis on 17 selected studies comprising 8505 alleles nationally showed that 52 mutations represented 97.5% of all the β thalassemia alleles with IVS I‐5 (G>C) varying from 44.8% in the north to 71.4% in the east …”

“…The distribution of mutations reported from different states in India has been collated in a few studies. [32][33][34] A meta-analysis on 17 selected studies comprising 8505 alleles nationally showed that 52 mutations represented 97.5% of all the β thalassemia alleles with IVS I-5 (G>C) varying from 44.8% in the north to 71.4% in the east. 33 There are a few recent reports of novel mutations as well like Codon 2 (−A), −42 (C>G), and −223 (T>C) from eastern India 35 and Codon 53 (C>T) from West Bengal.…”

ProfilingβThalassemia Mutations in Consanguinity and Nonconsanguinity for Prenatal Screening and Awareness Programme

“…Several previous reports from North India have emphasized the need for regular evaluation of the mutation, as the shift in the frequencies of the mutation is very high [ 5 , 6 , 8 , 9 ]. Thereby we have analyzed the spectrum of mutation in different neighboring states or country.…”

“…In India the social factors such as preference to marry within the community and among 1st degree relatives (consanguinity) is quite prevailing and thus plays an important role in increasing the gene pool of the mutation responsible for disease within the community [ 5 , 8 , 9 ]. In that scenario target oriented prenatal diagnosis helps early detection of the fetus status.…”