Spectrum of beta-thalassemia mutations in various regions of Punjab and Islamabad, Pakistan: establishment of prenatal diagnosis.

We present here an analysis of 888 unrelated beta-thal chromosomes consisting of 444 transfusion dependent children from various regions of Punjab and Islamabad Pakistan. By using Multiplex ARMS- PCR, restriction endonuclease analysis, allele specific oligonucleotide (ASO) hybridization and sequencing, 17 beta-thal mutations and 3 Hb variants were detected in 99.5 % (884/888) of the chromosomes analyzed. First trimester prenatal diagnosis by chorionic villus sampling (CVS) was also carried out in seven pregnancies at risk of beta-thalassemia. Our results indicate that three most common mutations accounted for 86.8% of the beta-thal alleles in this region. These findings have important implications for prevention of beta-thalassemia through genetic counseling and prenatal diagnosis in this part of Pakistan.