[A community-based genetic screening of large-scale population and prenatal diagnosis for alpha and beta thalassemia in Zhuhai city of Guangdong province].

OBJECTIVE: To describe a community-based model for prevention and control of severe alpha and beta thalassemias in Zhuhai city of Guangdong province. METHODS: Couples for premarital medical examination or regular healthcare examination in pregnancy were enrolled in this prospective screening program, which was supported by the two-level network composed of 6 local hospitals for testing thalassemias and follow-up for genetic counseling. A conventional heterozygote screening strategy was used to determine alpha and beta thalassemia traits in women and their partners according to the standard procedures of hematological phenotype analysis. Then confirmative diagnosis of alpha and beta thalassemia was performed on those couples suspected at-risk for severe thalassemia by using the PCR-based molecular diagnostic assays. The couples at-risk for severe thalassemia were counseled and offered prenatal diagnosis and termination of pregnancy in case of an affected fetus. RESULTS: During the period between January 1998 and December 2005, the screened records included 85522 young females and their partners for premarital screening and 10439 pregnant women for prenatal screening, with 71.38% coverage of total population recorded in this city for premarital screening. Six thousands five hundreds and sixty-three individuals in total were found to be the carriers of thalassemias, with 4312 for alpha thalassemia (4.5%) and 2251 for beta thalassemia (2.3%), respectively. One hundred and forty-eight couples were diagnosed to be at-risk for thalassemias, including 103 for alpha thalassemia and 45 for beta thalassemia, respectively. Successful prenatal diagnosis was made for 142 (98 for alpha thalassemia and 44 for beta thalassemia) out of 148 (95.9%) pregnancies at-risk for severe thalassemias. Twenty-three cases of hydrops fetalis, 4 of Hb H diseases and 14 of beta thalassemia were identified. All 41 pregnancies with affected fetuses were voluntarily terminated. Thus, this has led to a marked decrease of severe thalassemia syndrome since the program started. CONCLUSION: We presented the first community-based prospective screening program in China for control of alpha and beta thalassemia in Zhuhai city with a population of 1.29 million through premarital or prenatal screening. This model could be used for control of thalassemias and other hemoglobinopathies in other regions of China and also in other developing countries.

Carrier screening for alpha- and beta-thalassemia in pregnancy: the results of an 11-year prospective program in Guangzhou Maternal and Neonatal hospital.

OBJECTIVES: To evaluate the first prospective screening program in China for control of alpha and beta-thalassemia in the population of pregnant couples. METHODS: During the period between January 1993 and December 2003, a hospital-based preventive program was conducted at the biggest birth center in Guangzhou, with 1/17 of all deliveries in this city referred annually by use of conventional heterozygote screening strategy in combination with the system of regular healthcare examination in pregnancy. RESULTS: The screened records included 49 221 pregnant women, and 4503 husbands of the pregnant women showed positive on the screening test. Of the at-risk couples, there were 198 for alpha-thal (4.4%) and 83 for beta-thal (1.8%), respectively. Genetic counseling was offered to all at-risk couples and a successful prenatal diagnosis was performed for 269 out of 281 (95.7%) for alpha- or beta-thal major, with the remaining 12 couples refusing to accept prenatal diagnosis. Out of 187 pregnancies at risk for homozygous alpha0-thal and 82 at risk for beta-thal major, 51 hydrops fetalis with Hb Bart's and 18 beta-thal major were identified. All pregnancies with affected fetuses were voluntarily terminated, leading to a marked reduction of severe alpha- and beta-thal births at this hospital since the program has been launched. CONCLUSIONS: Our hospital-based program proved to be highly effective in reducing severe thals in pregnant populations.

Molecular epidemiological study of alpha- and beta-thalassemia in Sihui city.

OBJECTIVE: To investigate alpha- and beta-thalassemia (alpha- and beta-thal) gene frequencies and gene mutation spectrum in the population of Sihui City. METHODS: The umbilical cord blood samples from 1 007 neonates and peripheral blood samples from 1 524 apparently healthy adults for pre-marriage health check in Sihui city were collected for molecular epidemiologic study of alpha- and beta-thal respectively. The diagnostic standard for alpha-thal was the presence of Hb Bart's, and that for beta-thal was both the decrease of mean corpuscular volume (MCV<80 fl) and the increase of Hb A(2) level (> or = 3.5%). The samples of identified subjects with positive thal genotypes were further examined with PCR-based DNA analysis for determining the alpha- or beta-globin gene genotype, while those from subjects with positive genotypes but without mutations known to Chinese subjects were subjected to DNA sequence analysis of beta-globin gene. In addition, the alpha-thal alleles, -alpha(3.7) and -alpha(4.2) were examined in all umbilical cord blood samples. RESULTS AND CONCLUSION: Of all the 1 007 umbilical cord blood samples, 110 were identified as from alpha-thal gene carriers, 3 from patients Hb H disease and 1 from patients with hydrops fetalis, which meant an alpha-thal gene frequency of 11.72% (118/1 007). Three types of alpha-gene deletion were identified in this cohort, with the frequency of 53.4% (--SEA)), 34.7% (-alpha(3.7)) and 11.9% (-alpha(4.2)) respectively. By examining the peripheral venous blood samples from the 1,524 healthy adult subjects, 59 subjects were found to be beta-thal gene carriers with a rate of 3.87% (59/1,524), whose genotypes were determined and from whom 7 beta-thal mutations were identified. Of these 59 beta-thal gene carriers, 11 were diagnosed as having heterozygotes compound for beta- and alpha-thal genes with the deletion of the --(SEA) in 7 cases and -alpha(3.7) in 4 cases respectively, showing an incidence of 0.72% (11/1,524). The three commonest point mutations, beta CD41-42 (-CTTT) frameshift mutation, beta IVS2-654(C-->T) aberrant splicing mutation and beta-28 (A-->G) transcription mutation occurred with a total frequency of 84.75% among subjects with beta-thal allele mutations. In addition, a novel mutation, beta-globin gene promoter -90 (C-->T) allele was detected for the first time in Chinese subjects.