Clinical Hematological Characteristics Of Rare Hemoglobin Disease Mutation

Objectives: To study the mutation types and hematological characteristics of rare hemoglobin disease in Yunnan Province,and provide valuable data support for genetic consultation and prenatal diagnosis of hemoglobin disease.Meathods: From September 2018 to January 2020,people of childbearing age who went to the Medical Genetics Department of the First People’s Hospital of Yunnan Province to register personal information such as the ethnic origin of the patient,used second-generation sequencing to detect samples of rare hemoglobin disease mutations,and the mutation sites were verified by first-generation sequencing.The automatic blood cell analyzer was used for routine blood testing,and automatic capillary electrophoresis was used to detect hemoglobin components.Results: 23 rare hemoglobin mutation samples were collected,including 21 abnormal hemoglobin mutation samples and 2 new types of α-thalassemia.Of the 21 patients with abnormal hemoglobin disease,5 were male and 16 were female.A total of 12 mutation types of abnormal hemoglobin disease were detected,4 of which wereα-globin gene mutation types,including 3 cases of Hb Hekinan II heterozygous,2cases of Hb J-Broussais heterozygous,1 case of Hb Groene Hart heterozygous,and 1case of Hb Daneshgah-Tehran heterozygosity;8 types are β-globin gene types,including 3 cases of Hb New York heterozygous,3 cases of Hb Shizuoka heterozygous,3 cases of Hb J-Bangkok heterozygous,1 case of Hb Las Palmas heterozygosity,1 case of Hb Rush heterozygosity,1 case of Hb Agenogi heterozygosity,1 case of Hb J-Lome heterozygosity,and 1 case of Hb G-Coushatta heterozygosity.We identified two novel mutations in the two families: a missense mutation HBA2:c.245C>T and an intron deletion HBA2:c.95+11＿95+34del CTCCCCTGCTCCGACCCGGGCTCC.There were no abnormalities in erythrocyte parameters in 23 patients.Thehemoglobin electrophoresis results showed that 3 cases of Hb New York heterozygosity had a band of about 45.03% in Z11 region,and 3 cases of Hb J-Bangkok heterozygote had a band of about 52.60% in Z12 region.Two cases of Hb J-Broussais heterozygosity had a band of about 22.55% in Z12 area,one case of Hb Daneshgah-Tehran heterozygosity had a band of 24.5%,and one case of Hb Rush heterozygosity in Z11 area had 50.80%.Bands: 1 case of Hb Agenogi heterozygosity has a band of 39.60% in Z4 zone,1 case of Hb J-Lome heterozygosity has a band of50.80% in Z13 zone,and 1 case of Hb G-Coushatta e heterozygosity has in Z6 zone.40.80% of the bands,other abnormal hemoglobin mutation types of hemoglobin results were normal.Conclusion: There were no obvious anemia in the blood routine results of 23 patients.Eight kinds of abnormal hemoglobin heterozygous patients showed abnormal bands on capillary electrophoresis,and four kinds of abnormal hemoglobin heterozygous patients had abnormalities in capillary electrophoresis.Screening for abnormal hemoglobin disease only by blood routine and capillary electrophoresis will cause a certain missed rate.The heterozygotes of abnormal hemoglobin disease in this study have no obvious clinical symptoms,but when combined with other types of thalassemia,clinical manifestations of thalassemia may be manifested to varying degrees.These results improve genetic diagnostics for thalassemia,which can improve screening programs for silent thalassemia and prenatal diagnosis in the Chinese population.Therefore,our findings suggest that screening and detection of rare genetic mutations in abnormal hemoglobin disease should be strengthened.Prevention based on public education,population screening,and prenatal diagnosis is essential for the prevention and control of thalassemia in Yunnan Province.