DNAH5基因新型复合杂合变异所致Kartagener综合征患儿1例的临床及遗传学分析  

Genetic analysis of a child with Kartagener syndrome due to novel compound heterozygous variants of DNAH5 gene

作　　者：张珊 王朝兵 张勇[3] 胡言东 李旭 植创 Zhang Shan;Wang Chaobing;Zhang Yong;Hu Yandong;Li Xu;Zhi Chuang(Department of Pediatrics,Qionglai Maternal and Child Health Care Hospital,Qionglai,Sichuan 611530,China;Department of Radiology,Medical Center Hospital of Qionglai City,Qionglai,Sichuan 611530,China;Department of Pediatrics,Sichuan Provincial Maternity and Child Health Care Hospital,Chengdu,Sichuan 610031,China;Department of Radiology,Meishan Women and Children′s Hospital,Meishan,Sichuan 620010,China;Department of Ultrasonography,Qionglai Maternal and Child Health and Family Planning Service Center,Qionglai,Sichuan 611530,China)

机构地区：[1]邛崃市妇幼保健计划生育服务中心儿科,邛崃611530 [2]邛崃市医疗中心医院放射科,邛崃611530 [3]四川省妇幼保健院新生儿科,成都610031 [4]眉山市妇幼保健院放射科,眉山620010 [5]邛崃市妇幼保健计划生育服务中心超声科,邛崃611530

出　　处：《中华医学遗传学杂志》2023年第1期71-75,共5页Chinese Journal of Medical Genetics

摘　　要：目的分析1例Kartagener综合征(KTS)患儿的临床特征与遗传学病因。方法选取2020年10月于邛崃市妇幼保健院就诊的1例KTS患儿为研究对象。对患儿及其父母进行家系全外显子组测序以及生物信息学分析,通过Sanger测序进一步验证候选变异。模拟分析错义变异导致的蛋白结构改变,应用HSF 3.0在线平台对非编码区变异进行危害性预测。结果患儿具有支气管扩张、鼻窦炎及内脏反位等临床表现,基因检测提示其DNAH5基因存在c.5174T>C与c.7610-3T>G复合杂合变异,Sanger测序证实二者分别遗传自患儿母亲和父亲。两个变异在dbSNP、1000 Genomes、ExAC、ClinVar及HGMD等数据库中均未见收录。蛋白结构分析结果提示c.5174T>C(p.Leu1725Pro)可能影响蛋白局部结构的稳定性从而影响生物活性,HSF 3.0分析结果提示c.7610-3T>G可能破坏剪接受体从而影响转录。结论DNAH5基因c.5174T>C与c.7610-3T>G复合杂合变异可能是患儿的遗传学病因。上述发现进一步拓展了DNAH5基因的变异谱。Objective To explore the clinical characteristics and genetic basis of a child with Kartagener syndrome(KTS).Methods Trio-whole exome sequencing was carried out for the child and his parents,and candidate variants were verified by Sanger sequencing.Changes in protein structure due to missense variants were simulated and analyzed,and the Human Splicing Finder 3.0(HSF 3.0)online platform was used to predict the effect of the variant of the non-coding region.Results The child had featured bronchiectasis,sinusitis and visceral inversion.Genetic testing revealed that he has harbored compound heterozygous variants of the DNAH5 gene,namely c.5174T>C and c.7610-3T>G.Sanger sequencing confirmed the existence of the variants.The variants were not found in the dbSNP,1000 Genomes,ExAC,ClinVar and HGMD databases.Protein structural analysis suggested that the c.5174T>C(p.Leu1725Pro)variant may affect the stability of local structure and its biological activity.The results of HSF 3.0 analysis suggested that the c.7610-3T>G variant has probably destroyed a splicing receptor to affect the transcription process.Conclusion The compound heterozygous variants of the DNAH5 gene probably underlay the pathogenesis in the child.Above finding may facilitate the understanding of the clinical characteristics and genetic basis of KTS,and further expand the spectrum DNAH5 gene variants.

关 键 词：原发性纤毛运动障碍 KARTAGENER综合征 DNAH5基因 非编码区变异 

分 类 号：R725.9[医药卫生—儿科]