DNAH5基因新发移码变异所致1例原发性纤毛不动综合征患者的临床特征及遗传学分析
Clinical and genetic characteristics of a case of primary ciliary dyskinesia caused by new frameshift mutation of the DNAH5 gene
李孟阳 1黄珊 2马丽娜 3王岸聪3
作者信息
- 1. 山东第二医科大学临床医学院,山东潍坊 261053
- 2. 临沂市中医医院呼吸内科,山东临沂 276003
- 3. 临沂市人民医院生殖医学科,山东临沂 276000
- 折叠
摘要
目的:探讨1例原发性纤毛不动综合征(PCD)患者的临床特征和遗传学特点.方法:选取2020年7月于山东省临沂市人民医院生殖医学科门诊就诊的1例PCD患者为研究对象,收集患者的临床资料,应用全外显子组测序(WES)对患者进行基因检测,应用Sanger测序对候选变异进行验证.采用SWISS-MODEL进行预测变异基因的蛋白结构.结果:先证者存在慢性鼻炎、支气管扩张、内脏转位及男性不育的临床表型.先证者行WES检测显示DNAH5基因第74外显子存在c.12890dup(p.N4297Kfs*13)纯合移码变异,导致多肽链合成提前终止,对基因功能造成影响.SWISS-MODEL预测示突变后蛋白缺失了一部分氨基酸残基,导致蛋白3D构象发生变化.该变异在ClinVar、gnomAD及OMIM数据库中均未见收录.参照美国医学遗传学与基因组学学会相关指南,判定此变异为致病性变异(PVS1+PM2_P+PM3_P).结论:DNAH5基因c.12890dup(p.N4297Kfs*13)纯合移码变异可能是导致该患者临床表型的原因,上述发现丰富了 DNAH5基因的变异谱.
Abstract
Objective:To investigate the clinical and genetic characteristics of a case of primary ciliary dyskinesia(PCD).Methods:We collected the clinical data on a case of PCD treated in the Department of Reproductive Medicine of Linyi People's Hospi-tal in July 2020,detected the genes of the patient by whole-exome sequencing(WES),verified the candidate mutations by Sanger se-quencing,and predicted the protein structure of the mutant gene by SWISS-MODEL.Results:The proband was found with the clini-cal phenotypes of chronic rhinitis,bronchiectasis,visceral transposition and male infertility.WES revealed a homozygous frameshift variation of c.12890dup(p.N4297Kfs*13)in exon 74 of the DNAH5 gene,which led to the premature termination of polypeptide chain synthesis and affected the gene function.SWISS-MODEL prediction showed that some of the amino acid residues were deleted af-ter mutation,resulting in a 3D conformational change of the protein.This variation was not recorded in the ClinVar,gnomAD and OMIM databases and,according to the relevant guidelines of the American College of Genetics and Genomics,was classified as a path-ogenic variation(PVS1+PM2_P+PM3_P).Conclusion:The homozygous variation of the DNAH5 gene c.12890dup(p.N4297Kfs*13)may be the cause of the clinical phenotype of this case of PCD,and the above findings have enriched the variation spectrum of the DNAH5 gene.
关键词
DNAH5基因/原发性纤毛运动障碍/基因变异/男性不育Key words
DNAH5 gene/primary ciliary dyskinesia/genetic variation/male infertility引用本文复制引用
出版年
2024
NETL
NSTL
万方数据