MOLECULAR STUDY AND PRENATAL-DIAGNOSIS OF ALPHA-THALASSEMIA AND BETA-THALASSEMIA IN CHINESE

Thalassemia is one of the most common single gene diseases worldwide. Populations in southern China and Taiwan have high prevalence rates of ex-and beta-thalassemias. This review summarizes the current status o f molecular studies, carrier screening, and prenatal diagnosis of thal assemia in Chinese. There are three genotypes of alpha-thalassemia 1 a nd at least six of alpha-thalassemia 2 in Chinese. For alpha-thalassem ia 1, the South-East Asian deletion is the most common, followed by th e Thai then Philippine deletions. For alpha-thalassemia 2, the rightwa rd deletion is the most common, followed by the leftward deletion, and tile nondeletional defects Hb Constant Spring and Hb Quong Sze. Twent y-eight different beta-thalassemia mutations have been reported. Four mutations, IVS-II-654 (C-->T), codons 41/42 frameshift (-TCTT), and no nsense codons 17 (A-->T) and -28 (A-->G), account for more than 90% of mutant alleles. For detection of alpha-thalassemia, polymerase chain reaction-related techniques are mainly used. Southern blot hybridizati on is still useful, especially for prenatal diagnosis. For detection o f beta-thalassemia mutations,ns, analysis of amplification-created res triction sites and reverse dot blot hybridization have been extensivel y used. In Taiwan, a national screening program incorporating hematolo gical and molecular biological methods for thalassemia detection in pr egnant women has been in progress for 5 years. Prenatal diagnosis has been performed in more than 1,800 pregnancies, including 1,500 cases a t risk for homozygous alpha-thalassemia 1 and 300 for beta-thalassemia major, resulting in early prenatal diagnosis and termination of pregn ancies affected with homozygous alpha-thalassemia 1 and an approximate ly!; 70% decrease in the number of newborns affected with beta-thalass emia major. In mainland China, only one large-scale screening program is in place. Characterization of undefined alleles, a higher awareness of the disease among physicians and the general public, and improveme nt of the service;ice network will be important for early prenatal dia gnosis and prevention of the disease in the future.