| Background: Thalassemia is a kind of hemolytic anemia, characterized by the defective synthesis of a- and p-chains of hemoglobin. As one of the most common human monogenic hereditary diseases, a-thalassemia is widely spread throughout tropical areas, predominantly Southeast Asia, South China and a few African regions. (3-thalassemia is spread throughout the Mediterranean areas, Middle East, India, Pakistan, Southeast Asia, South China and North African regions. According to estimation of WHO, 4.5% of the world population carry a potentially pathological haemoglobinopathy gene. 300,000 infants are bom with major haemoglobin disorders, the most common being the thalassemia and sickle-cell disorder. The thalassemia syndromes are major public health problems in those high prevalence countries. Due to no ideal radical cure of thalassemia at present, the internationally recognized primary choice is to those fetuses with thalassemia major via prenatal gene diagnosis and selective abortions. So we carry out molecular epidomology of a- and P-thalassemia in Sihui city of Guangdong Province.Objective To make a preventive genetic program for controlling thalassemias, we process the study on the carrier rate and mutation spectrum of a- and p-thalassemias in Sihui city of Guangdong Province. Methods By using cluster sampling, 1,007 umbilical cord blood samples from neonates and 1,524 peripheral blood samples from apparently healthy young under pre-marriage consultation were collected for epidemiology survey of a-thalassemia and p-thalassemia, respectively. The local residents from this city were chosen to this study to obtain the data on the representative local population frequency. The phenotypic analysis was carried out by a complete blood count and hemoglobin electrophoresis for all samples collected. Thosewith Hb Bart's for a-thalassemia and those with both microcytosis (MCV<80 fL) and elevated levels of Hb A2 (≥3.5%) for P-thalassemia were subjected to genotyping of a- or P-globin gene using the PCR-based DNA analysis. In addition, the single a-globin gene deletions, -α3'7 and -α4.2 alleles, were defined in all umbilical cord blood samples for evaluating their gene frequencies. Results 110 a-thalassemia carriers, three patients with Hb H disease and one hydrops fetalis case were detected from 1,007 neonates, with a high a-thalassemia carrier rate of 11.72% (118 / 1,007). In this study, we have just characterized three types of a-thalassemia detions in the population and their constitutions are 53.4% (-SEA), 34.7% (-α37) and 11.9% (-α4.2), respectively. 59 p-thalassemia carriers were detected in 1,524 adult individuals and all phenotypic positive samples were found to be P-thalassemia mutations with seven mutants, with the p-thalassemia carrier rate of 3.87% (59 / 1,524). Of these 59 P-thalassemia carriers, eleven were diagnosed to co-inherit a-thalassemia in the form of the deletion of the -SEA (7 cases) or the -α3'7 (4 cases), with the testing rate of 0.72% (11 / 1,524). Our results showed that three commonest point mutations, βCD41-42 (-CTTT) frameshift mutation, PIVS2-654(C-T) aberrant splicing mutation and P-28 (A-G) transcription mutation accounted for 84.75% of the P-thalassemia alleles. In addition, a novel mutation, P-globin gene promoter -90 (C-T) allele was firstly reported in Chinese population. Conclusion In this study, we have demonstrated the approximate carrier frequency and detailed spectrum of a- and P-thalassemia in Sihui of Guangdong. The data obtained from this study will be of valuable reference to establish prevention program comprising of public education, a cost effective screening strategy, and adequate antenatal services for controlling thalassemias in this city.
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