中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
Chinese Journal of Medical Genetics
2015年
4期
515-519
,共5页
刘思平%宋兰林%熊丽%王克%申洪%钟梅
劉思平%宋蘭林%熊麗%王剋%申洪%鐘梅
류사평%송란림%웅려%왕극%신홍%종매
胎儿血红蛋白增高%α-珠蛋白基因拷贝数变异%多重探针连接扩增技术
胎兒血紅蛋白增高%α-珠蛋白基因拷貝數變異%多重探針連接擴增技術
태인혈홍단백증고%α-주단백기인고패수변이%다중탐침련접확증기술
Increased levels of fetal hemoglobin%Copy number variation in α-globin gene%Multiplex ligation-dependent probe amplification
目的 阐述α珠蛋白基因拷贝数丢失与增加对胎儿血红蛋白(fetal hemoglobin,HbF)水平的影响.方法 收集15例HbF增高合并β地中海贫血的患者,首先采用Gap-PCR检测常见α-地中海贫血的3种缺失型,之后应用多重探针连接扩增技术对α-珠蛋白基因簇行片段缺失与重复分析.结果 15例患者中,检出-SEA缺失杂合子3例,-α3.7缺失杂合子1例,-α4.2缺失纯合子1例,-α3.7与-SEA双重缺失杂合子1例,α珠蛋白基因簇大片段重复1例,类α-珠蛋白基因杂合缺失1例,7例样本未见α拷贝数的丢失与增加.结论 α拷贝数的增多会生成过多的α链,加重α与β链的不平衡性,同时过量的α链与γ链组成过多的HbF,导致HbF水平的升高;α拷贝数的减少会修正α与β链比例的失衡,减轻β0/β0或β0/β+的贫血症状,这类病例归为中间型β地中海贫血,一般具有较高的HbF水平.
目的 闡述α珠蛋白基因拷貝數丟失與增加對胎兒血紅蛋白(fetal hemoglobin,HbF)水平的影響.方法 收集15例HbF增高閤併β地中海貧血的患者,首先採用Gap-PCR檢測常見α-地中海貧血的3種缺失型,之後應用多重探針連接擴增技術對α-珠蛋白基因簇行片段缺失與重複分析.結果 15例患者中,檢齣-SEA缺失雜閤子3例,-α3.7缺失雜閤子1例,-α4.2缺失純閤子1例,-α3.7與-SEA雙重缺失雜閤子1例,α珠蛋白基因簇大片段重複1例,類α-珠蛋白基因雜閤缺失1例,7例樣本未見α拷貝數的丟失與增加.結論 α拷貝數的增多會生成過多的α鏈,加重α與β鏈的不平衡性,同時過量的α鏈與γ鏈組成過多的HbF,導緻HbF水平的升高;α拷貝數的減少會脩正α與β鏈比例的失衡,減輕β0/β0或β0/β+的貧血癥狀,這類病例歸為中間型β地中海貧血,一般具有較高的HbF水平.
목적 천술α주단백기인고패수주실여증가대태인혈홍단백(fetal hemoglobin,HbF)수평적영향.방법 수집15례HbF증고합병β지중해빈혈적환자,수선채용Gap-PCR검측상견α-지중해빈혈적3충결실형,지후응용다중탐침련접확증기술대α-주단백기인족행편단결실여중복분석.결과 15례환자중,검출-SEA결실잡합자3례,-α3.7결실잡합자1례,-α4.2결실순합자1례,-α3.7여-SEA쌍중결실잡합자1례,α주단백기인족대편단중복1례,류α-주단백기인잡합결실1례,7례양본미견α고패수적주실여증가.결론 α고패수적증다회생성과다적α련,가중α여β련적불평형성,동시과량적α련여γ련조성과다적HbF,도치HbF수평적승고;α고패수적감소회수정α여β련비례적실형,감경β0/β0혹β0/β+적빈혈증상,저류병례귀위중간형β지중해빈혈,일반구유교고적HbF수평.
Objective To detect copy number changes of α-globin gene,and analyze molecular mechanism of the impacts of fetal hemoglobin (HbF) levels for α-globin gene copy numbers loss or increase.Methods A total of 15 cases with combined increased levels of fetal hemoglobin with β thalassemia were collected.Firstly,three common α-thalassemia deletions were validated by Gap-PCR.Secondly,the largest deletions of the ββ-globin gene cluster were detected by multiplex ligation-dependent probe amplification (MLPA).Result Among the 15 cases,there was 1 case with duplication of the α-globin gene cluster,3 cases of SEA heterozygote deletion of the α-globin gene,1 cases of alpha 3.7 deletion heterozygote of the α-globin gene,1 case of alpha 4.2 deletion homozygote of the α-globin gene,1 case of deletion homozygote in the like α-globin gene.A compound heterozygous for SEA and alpha 3.7 of the α-globin gene was also detected.However,7 cases showed no copy numbers loss and increase of the the α-globin gene cluster.Conclusion Additional α-globin gene can produce excessive α-chain,which can aggravate imbalance for α and β-chain,and cause clinical symptoms in patients with ββ-thalassemia.Yet,copy number loss or mutation in α-globin gene will cause a milder clinical phenotype.
