PRENATAL AND MOLECULAR DIAGNOSIS OF BETA-THALASSEMIA MAJOR IN TAIWAN BY NATURALLY AND AMPLIFIED CREATED RESTRICTION SITES

To characterize mutations rapidly in 43 patients with beta-thalassemia major in Taiwan, we utilized a method of natural and amplified create d restriction site (ACRS) analysis for detection of beta-globin gene m utation. After analysis, eight different point mutations were found am ong 86 known chromosomes. IVS-2 nt 654 (C-->T), accounting for 40 of t he 86 mutations with mutant beta-globin genes, is the most common muta tion, followed by frameshift codons 41/42 (-TCTT) in 28 mutations, -28 mutation (A-->G) in 7 mutations, nonsense codon 17 (A-->T) in 5 mutat ions, frameshift codons 27/28 (insertion of C) in 2 mutations, IVS-1 n t 1 (G-->T) in 2 mutations, frameshift codons 71/72 (insertion of A) i n 1 mutation, and IVS-1 3' end TAG-->GAG in 1 mutation. The first four mutations account for 80 of all 86 mutations of beta-thalassemia majo r in Taiwan. Furthermore, the beta-globin gene mutation was identified successfully in one chorionic villi biopsy for prenatal diagnosis and in specimen of blood from one patient who had received bone marrow tr ansplantation (BMT). Complete diagnosis is possible in all of the Chin ese families with beta-thalassemia in Taiwan, and the first trimester prenatal diagnosis can be achieved simply by using only 13 oligonucleo tide primers and 10 restriction endonucleases. This non-radioactive as say was shown to be a rapid, sensitive, precise and safe method in det ecting the mutations of beta-thalassemia in Taiwan.