Gene Mutation Spectrum And Prenatal Diagnosis Of Thalassemia In Fujian Region

Objective: In order to provide effective suggestions for clinical genetic counseling and making prevention programs in Fujian province, this study investigated the type and frequency of gene variation in patients with thalassemia in Fujian population, and analyzed the characteristics of main gene variation and results of prenatal gene diagnosis by comparing with the other high-incidence regions in China.Methods: Blood counts and hemoglobin electrophoresis analysis were used to detect the thalassemia in peripheral blood samples of 14817 outpatients, which were collected from July 2008 to June 2014 in Fujian Provincial Maternity and Child Health Care Hospital.PCR and RDB were used to detect the common or deletion type of gene mutation, and new genetic types were further detected. The mutation frequencies were calculated and further compared to the distribution characteristics of six regions, including Guangdong, Guangxi, Hainan, Yunnan, Guizhou and Chongqing. In addition, the information related to the couple carriers with same type of thalassemia gene in Fujian region, who were adopted to prenatal diagnosis, were retrospectively analyzed. The above results were analyzed by SPSS17.0 statistical software.Results:1. 2747 cases of alpha thalassaemia were found in 14817 outpatients, accounting for 18.54%. Among them, a total of eight types of alpha thalassemia gene mutations, which are –SEA,-?3.7,-?4.2, ?WS?, ?CS?, ?WS?,--Thai and-HK?? according to the frequency from high to low, respectively. And the frequency of gene variation type is similar with Guangdong, Guangxi, Hainan and Yunnan regions.2. The analytic result of genotype and phenotype of hematology of 119 cases of Hb H patients shows that there was no significant difference in the hemoglobin content between in non-deletional genotype group(--SEA/-?CS?,--SEA/-?QS?,--SEA/-?WS?) and in deletional genotype group(--SEA/-?3.7 and--SEA/-?4.2), the mean corpuscular volume(MCV) and the mean corpuscular hemoglobin(MCH) in non-deletional genotype group was higher than that in deletional genotype group. However, when the number of--SEA/-?WS? cases were excluded, the Hb content in non-deletional genotype group was significantly lower than that in deletional genotype group, and the difference of MCV and MCH between the two groups did not change significantly.3. 1842 cases of alpha thalassaemia were found in 14817 outpatients, accounting for 12.43%. Among them, a total of eight types of beta thalassemia gene mutations, which are IVS-2-654(C?T), CD41-42(-TCTT), CD17(A?T),-28(A?G), CD27-28(+C), CD26(G?A), CD71-72(+A), CD43(G?T),-29(A?G), ATG?AGG, IVS-1-1(G?T), IVS-1-5(G?T), codon 36(-C), codon30(A?G), +22(G?A) and codons54-58(-TTATGGGCAACCC) according to the sequence from high to low, respectively. And the frequency of gene variation type is similar with Guangdong and Hainan regions, but different with Guangxi, Yunnan, Guizhou and Chongqing regions.4. 89 cases of alpha thalassaemia were found in 14817 outpatients, accounting for 0.60%. The result indicates that the incidence of composite thalassemia is low in Fujian region.5. In 247 cases of pregnant women for prenatal diagnosis, 7 cases choose Transabdominal Chorionic Villus Sampling in early stage, 186 underwent Amniotic Cavity Puncture Sampling, 54 underwent Percutaneous Umbilical Blood Sampling. Among them, a total of 7 cases with Hb H disease, 45 cases with Hb Bart's hydrops fetalis and 23 cases with heavy and middle type beta thalassemia were found.Conclusion:1. In a way, this study shows that the incidence of thalassemia in Fujian region is high, and the gene variation spectrum is complex, which has a certain similarity with Guangdong and Hainan regions.2. The gene variation frequency of alpha thalassemia is higher than that of beta in Fujian gegion. Meanwhile, some new genetic types were first found in our laboratory, such as codon 36(- C), codon 30(A?G), +22(G?A),--Thai and Hk??. The research results further complete the clinical data of genotype and hematology phenotype of thalassemia in Fujian region, which provides an important basis for marriage, childbearing and genetic counseling in Fujian Province.3. Prenatal diagnosis is an effective measure to avoid the children with heavy or middle type of thalassemia to be born, non-invasive prenatal diagnosis is a major trend of research and intervening thalassemia in the future.