MOLECULAR CHARACTERIZATION OF BETA-THALASSEMIA IN TAIWAN AND THE IDENTIFICATION OF 2 NEW MUTATIONS

Polymerase chain reaction-based techniques were used to study the mole cular defects of 480 unrelated beta-thalassemia heterozygotes in Taiwa n. Analysis of artificially created restriction sites and gap-polymera se chain reaction were performed to detect four common mutations, i.e. IVS-II-654 (C --> T), codons 41/42 (-TCTT), codon 17 (A --> T), -28 ( A --> G), and a deletional form of delta beta-thalassemia in the Chine se population. In cases with negative or ambiguous results with the af orementioned methods, direct DNA cycle sequencing using either S-35-dA TP or a fluorescent dye terminator, was carried out to determine the d efects. A total of 14 different mutations have been found in this seri es. The IVS-II-654 mutation was the most common (39.6%), followed by t he codons 41/42 mutation (37.9%). The four common genotypes accounted for 92.3% of defects. Two new mutations were detected: codon 31 (-C) a nd codons 40/41 (+T). Both defects resulted in a frameshift and a prem ature terminator, the former at codon 60, the latter at codon 43. Alth ough we have studied our cases extensively, the molecular defects in s even alleles are still unknown.