Prenatal diagnosis of ?-thalassaemia and other haemoglobinopathies in India

Abstract

This paper reports prenatal diagnosis of 787 fetuses of beta-thalassaemia and other haemoglobinopathies in Indian high-risk communities. DNA based diagnosis was offered in the first, as well as the second trimester, in 489 pregnancies (with five twins) on fetal tissues such as chorionic villus (CV) and amniocytes using the amplification refractory mutation system (ARMS) and restriction fragment length polymorphism (RFLP) techniques. Two hundred and ninety-two women (with one twin), who either presented late in the second trimester or whose DNA diagnosis was not informative, were offered prenatal diagnosis using globin chain synthesis (GCS) on fetal blood cells. Maternal contamination of fetal DNA was ruled out by variable number tandem repeat (VNTR) analysis using sites in four different genes (Apo-B, D1S-80, Ig-JH and Ha-ras), while contamination of fetal blood was checked by a particle size distribution channelyzer. Using both techniques we were able to offer complete diagnosis in 99.8% cases. Out of 494 fetuses tested by DNA analysis, 135 were found to be normal, 201 were carriers, whereas 146 were affected. Out of 293 fetuses analysed by GCS, 215 were unaffected and 71 were affected. In this study, both fetuses were tested in twin pregnancies, of which three required selective termination of one fetus. Because of social, religious taboos and family influences, genetic counselling was found to be an important guideline for couples selecting options for prenatal diagnosis. Our experience suggests that because of late presentation by many couples to the diagnostic centres, in developing countries like India, both the techniques of DNA analysis and GCS should be made available at major referral centres for maximum benefit to couples.

Screening for beta thalassaemia

“…Although the joint collaborative project provided some stimulus to the problem of thalassaemia in India and set up an excellent prevention centre in Mumbai,[15] a national prevention programme was not achieved. Twenty years later, statements stressing the importance of a prevention programme in India appear in the majority of thalassaemia screening and prenatal diagnosis publications from India.…”

“…The technology for prenatal diagnosis is available in many parts of India, but is carried out in an ad hoc manner, the majority of women already having an affected child. [1522–28]…”

Mutation Pattern in Beta Thalassaemia Trait Population: A Basis for Prenatal Diagnosis

“…Among these, prenatal diagnosis has been done all over the world where the problem of thalassaemia exists like Pakistan, India, Thailand, Iran, Cyprus and Turkey. [3][4][5][6][7][8][9][10] Cyprus had one of the highest carrier rates in the world, with an estimated carrier rate of one in seven but now there is not a single birth of thalassaemic child since last five years with the start of prenatal diagnosis and abortion of affected child with the parent's consent. 9 There has also been significant fall of births of thalassaemic children in Iran after the introduction of prenatal diagnosis and abortion made legal.…”

Financial Burden on the Families of Transfusion Dependent Thalassemic Children

“…There are about 25 million carrier of beta thalassemia genes and over 9000 children of thalassemia major born every year. (1,2) The mainstay of the supportive treatment of thalassemia major is regular blood transfusion accompanied by iron chelating therapy. Hematopoietic stem cell transplantation, a curative therapy costs Rupees (Rs) one million which is very expensive and few can afford.…”