原发性纤毛运动障碍家系PIH1D3基因的变异分析  

Analysis of PIH1D3 variant in a Chinese pedigree affected with primary ciliary dyskinesia

作　　者：王闪[1] 李冰[1] 陈亚飞[1] 周正[2] 鲍瑞玲[1] Wang Shan;Li Bing;Chen Yafei;Zhou Zheng;Bao Ruiling(Department of Laboratory Medicine,Xinxiang Central Hospital,Xinxiang,Henan 453000,China;Department of Respiratory and Critical Medicine,the Second Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450014,China)

机构地区：[1]新乡市中心医院检验科,河南453000 [2]郑州大学第二附属医院呼吸与急危重症医学科,450014

出　　处：《中华医学遗传学杂志》2020年第9期1021-1024,共4页Chinese Journal of Medical Genetics

基　　金：河南省教育厅科学技术研究重点项目(14A310016)。

摘　　要：目的探讨1个原发性纤毛运动障碍(primary ciliary dyskinesia,PCD)家系PIH1D3基因的变异及其基因型与表型的对应关系。方法对一例临床确诊的PCD患者进行家系分析,观察其鼻腔粘膜纤毛及精子鞭毛的超微结构,同时对患者的DNA样本进行全外显子组测序。结果患者及其家系患者均有不同程度的呼吸道感染史,2人具有内脏异位,表现为右位心,1例表现为不育。患者的纤毛及鞭毛结构存在异常,表现为内、外侧动力蛋白臂缺失,纤毛排列紊乱。DNA测序发现患者携带PIH1D3基因致病变异c.355C>T,该变异位于关键的PIH1结构域,所对应的氨基酸序列在人、猕猴、家犬、小鼠、爪蟾及斑马鱼中高度保守。结论PIH1D3基因的缺失可导致鼻腔纤毛及精子鞭毛中内、外侧动力蛋白臂组装失败、纤毛及精子无法正常游动等典型的PCD表型,临床可借助基因检测提高PCD的检出率。Objective To detect variant of PIH1D3 gene in a Chinese pedigree affected with primary ciliary dyskinesia(PCD)and explore its genotype-relationship correlation.Methods PCD patients from the pedigree were analyzed.Ultrastructures of the cilia and flagella of the nasal mucosa were analyzed.DNA samples of the patients were sequenced.Results The proband and all other affected members of his pedigree had a history of various degree of respiratory tract infection.Two patients had visceral heterotopia,and one was infertile.Electronic microscopy revealed abnormal structures of cilia and flagella.The inner and outer dynein arms were missing,and the arrangement of cilia was disordered.DNA sequencing showed that all patients have carried a c.355C>T variant of the PIH1D3 gene.The corresponding nucleotide was located in a key PIH1 domain,and the site is highly conserved among human,macaque,domestic dog,mouse,xenopus and zebrafish.Conclusion Deletion of the PIH1D3 gene can lead to failure of assembly of inner and outer dynein arms in nasal cilia and sperm flagella,and failure of normal swimming of cilia and sperm.The diagnosis rate of PCD can be validated by genetic testing.

关 键 词：PIH1D3基因 原发性纤毛运动障碍 分子机制 

分 类 号：R596.1[医药卫生—内科学] R440[医药卫生—临床医学]