Analysis Of Gene Mutation Types Of Thalassemia In 228 Children Aged 0-18 In Luzhou,Sichuan Province

Objective:thalassemia which is the most common and highest incidence in the world is a single gene hereditary hemolytic anemia and also one of the serious harm of hemoglobin disease.Due to the defect of globin gene,the resultant reduction or loss of the protein peptide chain is caused.Thalassemia is widely distributed in the World,according to statistics,about 5percent of the global population carry with the hemoglobin disease geneIn the global,Guangdong,Guangxi,Hainan and other southern regions have high incidence.Because of the diversity of globin gene mutations,the gene type is different,and its clinical manifestation is also uneven,Heavy Mediterranean anemia,there is no economic and effective treatment strategy,can only rely on regular blood transfusion and removing iron to maintain life,and it not only imposes immeasurable burdens on families and society,but also seriously threatens the health of human life.Therefore,genetic counselling and prenatal diagnosis is generally accepted as an effective method to reduce the incidence of thalassemia.this study aims to explore the types of gene mutation and frequency ofαandβ-thalassemia in 228 cases aged 0 to 18 years in Luzhou,Sichuan Province to provide a theoretical reference for the development of thalassemia genetic counseling and prevention programs in Luzhou area.Methods:1.Cases source:between January 2013 and December 2015,children by the four county areas of Luzhou City transferred to the Affiliated Hospital of Southwest Medical university of hematologic abnormalities and had ruled out iron deficiency anemia and other diseases.The child belongs to luzhou household register.2.Children who have content of hemoglobin（Hb）<110 g/L,and the average red blood cell volume（MCV）<80 fl,the average amount of red blood cell hemoglobin（MCH）<27 pg should test hemoglobin electrophoresis,and Alpha-thalassaemia test positive was HbA2<2.5%and/or HbH,HbBart’s or HbCS,with no other abnormal Hb bands,beta thalassemia test positive was HbA2>3.5%and/or HbF>2%.3.The three missing alpha-thalassaemia,including--^SEA、-α^3.7、-α^4.2,were detected with gap-PCR,The PCR-RDB was used to detect 8 common and 9 rare mutation types in China,including CD41-42（-CTTT）,CD17（AAG>TAG）,IVS-II-654（C>T）,CD43（G-T）,-29（A-G）,-28（A-G）,CD71-72（+A）,beta E,CD14-15（+G）,CD27-28（+C）,IVS-1-1（G-T）,IVS-1-5（G-C）,CD31（-C）,-30（T-C）,-32（C-A）,Int（ATG>AGG）,Cap（-AAAC）.Results:1.39α-thalassaemia and 189β-thalassaemia patients were detected among 382 examiners,meanwhile,the prevalence were 10.21%and 49.47%.2.5 types of mutation genotypes and 3different mutation were identified in 39 cases ofα-thalassaemia,A total of 6cases of thalassaemia with static type alpha includeαα/-α^3.7（12.82%）andαα/-α^4.2（2.56%）;16 cases of light alpha Mediterranean anemia includeαα/--^SEA（41.02%）;There were 17 cases of intermediate alpha-mediterranean anemia including-α^3.7/--^SEA（33.33%）and-α^4.2/--^SEA（10.27%）,and the frequency ofαα/--^SEA was the higtest.3.8 different mutation and 13 different genetypes were detecated in 189 cases ofβ-thalassaemia,the mutations were detected by CD17,cd41-42,ivs-ii-654,-28,cd14-15,cd71-72,CD43,and beta E,respectively accounting for 44.04%,25.39%,21.76%,3.62%,2.07%,1.55%,1.03%,0.52%.the top three in sequences are CD17（A-T）（44.04%）、CD41-42（-TCTT）（25.39%）、IVS-II-654（C-T）（21.76%）,among 183 cases of heterozygote and 6 cases of double heterozygotes,the heterozygote has the highest percentage.Conclusion:1.The detection rate of beta thalassemia in luzhou region is higher than that of alpha-thalassaemia.The most common mutations of the beta thalassemia gene are CD17（A-T）、CD41-42（-TCTT）、IVS-II-654;The missing alpha thalassaemia mutant gene is the most common in SEA.2.It can quickly and accurately detect the common thalassaemia mutated gene and has good clinical application value.3.genetic counselling and early prenatal diagnosis have important implications for the prevention and intervention of birth defects in thalassaemia.