Early prenatal diagnosis of beta-thalassaemia in Singapore
Ng, I.S.; Ong, J.B.; Tan, C.L.; Law, H.Y.
Annals of the Academy of Medicine Singapore 25(6): 779-782
1996
ISSN/ISBN: 0304-4602 PMID: 9055002 Document Number: 460061
beta-thalassaemia is one of the commonest autosomal recessive genetic diseases in the Singapore population. In the homozygous form, it results in a severe anaemia, requiring monthly blood transfusion for survival. Because of the less than satisfactory treatment available for the condition, prenatal diagnosis has always been an option for couples at-risk. The available method was globin chain analysis of foetal blood, obtained at 18 to 20 weeks of gestation. Affected pregnancies would then be diagnosed and require termination in the mid to late second trimester. A relatively newer technique, chorionic villus sampling (CVS), allows foetal material to be obtained in the first trimester. However, analysis of the foetal tissue requires direct gene studies to be performed. The aim of this study was to evaluate the feasibility of this analysis in couples at-risk for beta-thalassaemia in Singapore. Sixteen couples who were at-risk for a child with beta-thalassaemia major were offered prenatal diagnosis. All of them opted for CVS as compared to foetal blood sampling. The mutations in the beta-globin gene in these couples at-risk were identified. Direct gene analysis was then performed on the foetal sample, using a variety of molecular techniques. These included reverse dot-blot hybridization, allele-specific oligonucleotide hybridization, restriction enzyme digests and direct analysis of amplified products. DNA profiling was done for each case to exclude definitively the possibility of maternal tissue contaminating the foetal sample. The results in all these cases were unequivocal. The procedure of CVS itself was uneventful in these 16 couples. Procedural-associated foetal loss was nil. Prenatal diagnosis in the first trimester allows early termination of an affected pregnancy with significantly less maternal morbidity and parental anxiety. It also results in greater patient acceptability of the procedure and plays a key role in the prevention of this devastating genetic disease.