DNAH5基因新发突变致原发性纤毛运动障碍1例

doi:10.6040/j.issn.1671-7554.0.2022.0205

摘要/Abstract

摘要： 目的探讨DNAH5基因突变所致原发性纤毛运动障碍(PCD)的临床特点、诊治方法,以提高对该病的认识。方法回顾性分析山东大学齐鲁医院(青岛)收治的1例儿童PCD患者的临床资料,包括主要症状、化验检查、影像学表现、基因检测、透射电镜(TEM)检查结果及诊疗过程。结果该患儿有新生儿期呼吸窘迫、婴儿期开始出现的反复咳嗽咳痰、支气管扩张及慢性鼻窦炎等PCD特征性表现,支气管黏膜TEM检查未见纤毛结构,全外显子测序提示DNAH5基因存在致病性复合杂合变异, PCD诊断明确。急性期给予抗感染及气道廓清治疗,并定期随访。结论 PCD临床表现多样,缺乏单一的特异性诊断方法,对可疑的患者需综合分析高速摄像显微分析、免疫荧光分析、TEM以及基因检测等多种检查结果,进一步确定诊断。目前PCD尚无治愈方法,治疗目的主要为延缓疾病进展。

关键词: 原发性纤毛运动障碍, 支气管扩张, 慢性鼻窦炎, 透射电镜, 基因检测

Abstract: Objective To explore the clinical characteristics, diagnosis and treatment of primary ciliary dyskinesia(PCD)caused by DNAH5 gene mutation. Methods The clinical data of a child with PCD admitted to our hospital were retrospectively analyzed, including the main symptoms, laboratory examination results, imaging findings, gene detection results, transmission electron microscopy(TEM)results and the diagnosis and treatment progress. Results The child had respiratory distress in the neonatal period; repeated cough, sputum, bronchiectasis and chronic sinusitis in infancy. TEM of bronchial mucosa revealed no cilium and the whole exon sequencing indicated a pathogenic compound heterozygous mutation of DNAH5 gene. The diagnosis of PCD was confirmed. Anti-infection and airway clearance therapy were given in the acute stage, and regular follow-up was performed. Conclusion PCD has a variety of clinical manifestations and lacks a single specific diagnosis test. For suspicious patients, a comprehensive analysis of high-speed video microscopy, immunofluorescence microscopy, TEM and gene detection is required to confirm the diagnosis. Currently, there is no cure for PCD, the aim of treatment is to delay the progression of the disease.

Key words: Primary ciliary dyskinesia, Bronchiectasis, Chronic sinusitis, Transmission electron microscopy, Gene detection

中图分类号:

R725

王陆敏,周士英,黄启坤,刘艳丽. DNAH5基因新发突变致原发性纤毛运动障碍1例[J]. 山东大学学报 (医学版), 2022, 60(8): 103-108.

WANG Lumin, ZHOU Shiying, HUANG Qikun, LIU Yanli. A case of primary ciliary dyskinesia caused by a novel DNAH5 gene mutation[J]. Journal of Shandong University (Health Sciences), 2022, 60(8): 103-108.

参考文献

[1] Lucas JS, Davis SD, Omran H, et al. Primary ciliary dyskinesia in the genomics age[J]. Lancet Respir Med, 2020, 8(2): 202-216.
[2] Hannah WB, Seifert BA, Truty R, et al. The global prevalence and ethnic heterogeneity of primary ciliary dyskinesia gene variants: a genetic database analysis[J]. Lancet Respir Med, 2022, 10(5): 459-468.
[3] Mullowney T, Manson D, Kim R, et al. Primary ciliary dyskinesia and neonatal respiratory distress[J]. Pediatrics, 2014, 134(6): 1160-1166.
[4] 张静, 白银, 尤少华, 等. Kartagener综合征合并分泌性中耳炎患者的基因诊断[J].中华耳科学杂志, 2014, 12(1): 41-44. ZHANG Jing, BAI Yin, YOU Shaohua, et al. Gene diagnosis in patients with Kartagener syndrome induced chronic secretory otitis media[J]. Chinese Journal of Otology, 2014, 12(1): 41-44.
[5] Rollin M, Seymour K, Hariri M, et al. Rhinosinusitis, symptomatology & absence of polyposis in children with primary ciliary dyskinesia[J]. Rhinology, 2009, 47(1): 75-78.
[6] Lucas JS, Barbato A, Collins SA, et al. European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia[J]. Eur Respir J, 2017, 49(1): 1601090.
[7] Shapiro AJ, Davis SD, Polineni D, et al. Diagnosis of primary ciliary dyskinesia. An official American Thoracic Society Clinical Practice Guideline[J]. Am J Respir Crit Care Med, 2018, 197(12): e24-e39.
[8] 中国罕见病联盟呼吸病学分会,原发性纤毛运动障碍诊断与治疗中国共识专家组. 原发性纤毛运动障碍诊断与治疗中国专家共识[J]. 上海医学, 2020, 43(4): 193-202.
[9] 中华医学会儿科学分会呼吸学组疑难少见病协作组,国家呼吸系统疾病临床医学研究中心,《中华实用儿科临床杂志》编辑委员会. 儿童原发性纤毛运动障碍诊断与治疗专家共识[J]. 中华实用儿科临床杂志,2018, 33(2): 94-99.
[10] Wallmeier J, Nielsen KG, Kuehni CE, et al. Motile ciliopathies[J]. Nat Rev Dis Primers, 2020, 6(1): 77.
[11] 王昊, 徐保平. 儿童原发性纤毛运动障碍遗传发病机制与基因诊断研究进展[J].中华实用儿科临床杂志, 2021, 36(10): 786-789. WANG Hao, XU Baoping. Research progress on genetic pathogenesis and gene diagnosis of primary ciliary dyskinesia in children[J]. Chin J Appl Pediatr, 2021, 36(10): 786-789.
[12] 王珂, 陈星, 郭春艳. 等. 原发性纤毛运动障碍三例纤毛结构与基因变异并文献复习[J].中华儿科杂志, 2018, 56(2): 134-137. WANG Ke, CHEN Xing, GUO Chunyan, et al. Cilia ultrastructural and gene variation of primary ciliary dyskinesia: report of three cases and literatures review[J]. Chin J Pediatr, 2018, 56(2): 134-137.
[13] Guo T, Tan ZP, Chen HM, et al. An effective combination of whole-exome sequencing and runs of homozygosity for the diagnosis of primary ciliary dyskinesia in consanguineous families[J]. Sci Rep, 2017, 7(1): 7905.
[14] 李莹, 付文龙, 田代印, 等. 基因检测确诊纤毛结构正常的原发性纤毛运动障碍2例病例报告[J].中国循证儿科杂志, 2020, 15(5): 394-396.
[15] Sui W, Hou X, Che W, et al. CCDC40 mutation as a cause of primary ciliary dyskinesia: a case report and review of literature[J]. Clin Respir J, 2016, 10(5): 614-621.
[16] Liu L, Luo H. Whole-exome sequencing identified a novel compound heterozygous mutation of LRRC6 in a Chinese primary ciliary dyskinesia patient[J]. Biomed Res Int, 2018, 2018: 1854269. doi: 10.1155/2018/1854269.
[17] Li Y, Jiang C, Zhang X, et al. The effect of a novel LRRC6 mutation on the flagellar ultrastructure in a primary ciliary dyskinesia patient[J]. J Assist Reprod Genet, 2021, 38(3): 689-696.
[18] Guan Y, Yang H, Yao X, et al. Clinical and genetic spectrum of children with primary ciliary dyskinesia in China[J]. Chest, 2021, 159(5): 1768-1781.
[19] Liu L, Zhou K, Song Y, et al. CCDC40 mutation as a cause of infertility in a Chinese family with primary ciliary dyskinesia[J]. Medicine, 2021, 100(51): e28275.
[20] Dai HL, Wang D, Guang XF, et al. Pulmonary hypertension in a patient with Kartagener’s syndrome and a novel homozygous nonsense mutation in CCDC40 gene: a case report[J]. Front Med(Lausanne), 2022, 9: 860684. doi: 10.3389/fmed.2022.860684.
[21] Wang L, Zhao X, Liang H, et al. Novel compound heterozygous mutations of DNAH5 identified in a pediatric patient with Kartagener syndrome: case report and literature review[J]. BMC Pulm Med, 2021, 21(1): 263.
[22] Guo Z, Chen W, Wang L, et al. Clinical and genetic spectrum of children with primary ciliary dyskinesia in China[J]. J Pediatr, 2020, 225: 157-165.e5. doi: 10.1016/j.jpeds.2020.05.052.
[23] Xu X, Gong P, Wen J. Clinical and genetic analysis of a family with Kartagener syndrome caused by novel DNAH5 mutations[J]. J Assist Reprod Genet, 2017, 34(2): 275-281.
[24] Kobbernagel HE, Buchvald FF, Haarman EG, et al. Efficacy and safety of azithromycin maintenance therapy in primary ciliary dyskinesia(BESTCILIA): a multicentre, double-blind, randomised, placebo-controlled phase 3 trial[J]. Lancet Respir Med, 2020, 8(5): 493-505.
[25] Davis SD, Rosenfeld M, Lee HS, et al. Primary ciliary dyskinesia: longitudinal study of lung disease by ultrastructure defect and genotype[J]. Am J Respir Crit Care Med, 2019, 199(2): 190-198.
[26] Frija-Masson J, Bassinet L, Honoré I, et al. Clinical characteristics, functional respiratory decline and follow-up in adult patients with primary ciliary dyskinesia[J]. Thorax, 2017, 72(2): 154-160.

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