摘要
目的报告1例由罕见变异导致的重型血友病A(hemophilia A,HA),并探讨大片段重复变异的致病机制。方法先后进行F8基因第22内含子及第1内含子倒位检测、Sanger测序以及多重连接探针扩增(multiple ligation-dependent probe amplification,MLPA)检测。检索HA基因变异数据库并分析患者的临床特征。结果先证者FⅧ活性(FⅧ∶C)为0.3%,为重型HA,抑制物检测为阴性。倒位检测及Sanger测序均未发现变异,MLPA检测提示先证者存在Ex 1_22 dup(2 copies)半合变异;其母亲FⅧ∶C 60%,为携带者[Ex 1_22 dup(3 copies)]。HA基因变异数据库所收录的24例大片段重复变异均表现为重型HA,仅1例为抑制物阳性史。结论大片段重复变异可导致重型HA。MLPA能够有效提高HA患者基因变异的检出率。
Objective To report on a case with severe hemophilia A(HA)caused by a large duplication of F8 gene.Methods Inversion detection,Sanger sequencing,and multiplex ligation-dependent probe amplification(MLPA)were used to detect the mutation in the proband and his mother.Results The patient,a 7-year-old boy,was diagnosed with severe HA at 8 months.No inhibitor was developed over 150 exposure days.Intronic inversion detection and Sanger sequencing have failed to identify pathogenic variants,while MLPA revealed a large duplication[Ex 1_22 dup(2 copies)]in the proband,for which his mother was a carrier[Ex 1_22 dup(3 copies)].Large duplications of the F8 gene have so far been found in 24 HA patients,all of whom had a severe phenotype,only one had a history of inhibitors.Conclusion Large duplications of F8 gene are associated with severe HA.The diagnostic rate for HA may be increased by MLPA.
作者
王稳
崔东艳
蒋丽娟
张艾
刘爱国
胡群
Wang Wen;Cui Dongyan;Jiang Lijuan;Zhang Ai;Liu Aiguo;Hu Qun(Department of Pediatric Hematology,Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology,Wuhan,Hubei 430030,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2022年第1期72-75,共4页
Chinese Journal of Medical Genetics
基金
HERO(Haemophilia Experiences,Results,and Opportunities)基金。
