<i>DNAH5</i>基因在慢性肺部疾病中的作用_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

馬慧琳 ¹ , 郭潤蓉 ² , 劉瑞云 ³ , 王瑤瑤 ¹ , 于新娟 ⁴ ,  韓偉 ⁵

1. ;
2. ;
3. ;
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5. ;

Corresponding?author：

韓偉, Email: sallyhan1@163.com

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DOI：

10.7507/1671-6205.202501026

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Citation： 馬慧琳, 郭潤蓉, 劉瑞云, 王瑤瑤, 于新娟, 韓偉. DNAH5基因在慢性肺部疾病中的作用. Chinese Journal of Respiratory and Critical Care Medicine, 2025, 24(11): 816-820. doi: 10.7507/1671-6205.202501026 Copy

1.	Olbrich H, H?ffner K, Kispert A, et al. Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry. Nat Genet, 2002, 30: 143-144.
2.	Iba?ez-Tallon I, Heintz N & Omran H. To beat or not to beat: roles of cilia in development and disease. Hum Mol Genet, 2003, 12: R27-R35.
3.	Mitchison HM, Valente EM. Motile and non-motile cilia in human pathology: from function to phenotypes. J Pathol, 2017, 241(2): 294-309.
4.	Hornef N, Olbrich H, Horvath J, et al. DNAH5 mutations are a common cause of primary ciliary dyskinesia with outer dynein arm defects. Am J Respir Crit Care Med, 2006, 174: 120-126.
5.	Oltean A, Schaffer AJ, Bayly PV, et al. Quantifying ciliary dynamics during assembly reveals stepwise waveform maturation in airway cells. Am J Respir Cell Mol Biol, 2018, 59: 511-522.
6.	Zheng R, Yang W, Wen Y, et al. Dnah9 mutant mice and organoid models recapitulate the clinical features of patients with PCD and provide an excellent platform for drug screening. Cell Death Dis, 2022, 13: 559.
7.	El Zein L, Omran H, Bouvagnet P. Lateralization defects and ciliary dyskinesia: lessons from algae. Trends Genet, 2003, 19(3): 162-167.
8.	Emiralio?lu N, Ta?k?ran ZE, Ko?ukcu C, et al. Genotype and phenotype evaluation of patients with primary ciliary dyskinesia: First results from Turkey. Pediatr Pulmonol, 2020, 55: 383-393.
9.	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. BMC Pulm Med, 2021, 21: 263.
10.	Chen W, Guo Z, Li M, et al. Next-generation sequencing-based copy number variation analysis in chinese patients with primary ciliary dyskinesia revealed novel DNAH5 copy number variations. Phenomics, 2024, 4: 24-33.
11.	Kispert A, Petry M, Olbrich H, et al. Genotype-phenotype correlations in PCD patients carrying DNAH5 mutations. Thorax, 2003, 58: 552-554.
12.	Zariwala MA, Knowles MR, Omran H. Genetic defects in ciliary structure and function. Annu Rev Physiol, 2007, 69: 423-450.
13.	Yang W, Chen L, Guo J, et al. Multiomics analysis of a DNAH5-mutated PCD organoid model revealed the key role of the TGF-β/BMP and notch pathways in epithelial differentiation and the immune response in DNAH5-mutated patients. Cells, 2022, 11(24): 4013.
14.	Chalmers JD, Hill AT. Mechanisms of immune dysfunction and bacterial persistence in non-cystic fibrosis bronchiectasis. Mol Immunol, 2013, 55(1): 27-34.
15.	Chen ZG, Li YY, Wang ZN, et al. Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis. J Thorac Dis, 2018, 10(3): 1753-1764.
16.	Puchelle E, Zahm JM, Tournier JM, et al. Airway epithelial repair, regeneration, and remodeling after injury in chronic obstructive pulmonary disease. Proc Am Thorac Soc, 2006, 3(8): 726-733.
17.	Coraux C, Roux J, Jolly T, et al. Epithelial cell-extracellular matrix interactions and stem cells in airway epithelial regeneration. Proc Am Thorac Soc, 2008, 5(6): 689-694.
18.	T?zser J, Earwood R, Kato A, et al. TGF-β signaling regulates the differentiation of motile cilia. Cell Rep, 2015, 11: 1000-1007.
19.	Glaser L, Coulter PJ, Shields M, et al. Airway epithelial derived cytokines and chemokines and their role in the immune response to respiratory syncytial virus infection. Pathogens, 2019, 8(3): 106.
20.	Yang SC, Chang SH, Hsieh PW, et al. Dipeptide HCH6-1 inhibits neutrophil activation and protects against acute lung injury by blocking FPR1. Free Radic Biol Med, 2017, 106: 254-269.
21.	McElvaney OJ, McEvoy NL, McElvaney OF, et al. Characterization of the inflammatory response to severe COVID-19 illness. Am J Respir Crit Care Med, 2020, 202(6): 812-821.
22.	Yeleswaram S, Smith P, Burn T, et al. Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment. Clin Immunol, 2020, 218: 108517.
23.	Goutaki M, Meier AB, Halbeisen FS, et al. Clinical manifestations in primary ciliary dyskinesia: systematic review and meta-analysis. Eur Respir J, 2016, 48: 1081-1095.
24.	Wallmeier J, Nielsen KG, Kuehni CE, et al. Motile ciliopathies. Nat Rev Dis Primers, 2020, 6: 77.
25.	Knowles MR, Zariwala M, Leigh M. Primary ciliary dyskinesia. Clin Chest Med, 2016, 37(3): 449-461.
26.	Knowles MR, Daniels LA, Davis SD, et al. Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease. Am J Respir Crit Care Med, 2013, 188: 913-922.
27.	Djakow J, Svobodová T, Hrach K, et al. Effectiveness of sequencing selected exons of DNAH5 and DNAI1 in diagnosis of primary ciliary dyskinesia. Pediatr Pulmonol, 2012, 47: 864-875.
28.	Zhao X, Bian C, Liu K, et al. Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia. Orphanet J Rare Dis, 2021, 16: 293.
29.	de Ceuninck van Capelle C, Luo L, Leitner A, et al. Proteomic and structural comparison between cilia from primary ciliary dyskinesia patients with a DNAH5 defect. Front Mol Biosci, 2025, 12: 1593810.
30.	Lucas JS, Barbato A, Collins SA, et al. European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Eur Respir J, 2017, 49(1): 1601090.
31.	Black HA, de Proce SM, Campos JL, et al. Whole genome sequencing enhances molecular diagnosis of primary ciliary dyskinesia. Pediatr Pulmonol, 2024, 59: 3322-3332.
32.	Lai M, Pifferi M, Bush A, et al. Gene editing of DNAH11 restores normal cilia motility in primary ciliary dyskinesia. J Med Genet, 2016, 53(4): 242-249.
33.	Chalmers JD, Chang AB, Chotirmall SH, et al. Bronchiectasis. Nat Rev Dis Primers, 2018, 4: 45.
34.	Gao YH, Guan WJ, Liu SX, et al. Aetiology of bronchiectasis in adults: a systematic literature review. Respirology, 2016, 21: 1376-1383.
35.	Boyton RJ, Altmann DM. Bronchiectasis: current concepts in pathogenesis, immunology, and microbiology. Annu Rev Pathol, 2016, 11: 523-554.
36.	Guan WJ, Li JC, Liu F, et al. Next-generation sequencing for identifying genetic mutations in adults with bronchiectasis. J Thorac Dis, 2018, 10: 2618-2630.
37.	Morillas HN, Zariwala M, Knowles MR. Genetic causes of bronchiectasis: primary ciliary dyskinesia. Respiration, 2007, 74: 252-263.
38.	Zhang RL, Pan CX, Tang CL, Cen LJ, et al. Motile ciliary disorders of the nasal epithelium in adults with bronchiectasis. Chest, 2023, 163(5): 1038-1050.
39.	Cloutier MM, Baptist AP, Blake KV, et al. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol, 2020, 146: 1217-1270.
40.	Kovacic MB, Myers JM, Wang N, et al. Identification of KIF3A as a novel candidate gene for childhood asthma using RNA expression and population allelic frequencies differences. PLoS One, 2011, 6(8): e23714.
41.	Wang T, He C, Wu H, et al. Subtyping children with asthma by clustering analysis of mRNA expression data. Front Genet, 2022, 13: 974936.
42.	Shigemasa R, Masuko H, Oshima H, et al. The primary ciliary dyskinesia-related genetic risk score is associated with susceptibility to adult-onset asthma. PLoS One, 2024, 19: e0300000.
43.	Corcoran TE, Huber AS, Hill SL, et al. Mucociliary clearance differs in mild asthma by levels of type 2 inflammation. Chest, 2021, 160: 1604-1613.
44.	Mak ACY, White M, Eckalbar WL, et al. Whole-genome sequencing of pharmacogenetic drug response in racially diverse children with asthma. Am J Respir Crit Care Med, 2018, 197(12): 1552-1564.
45.	Agustí A, Celli BR, Criner GJ, et al. Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary. Eur Respir J, 2023, 61(4): 2300239.
46.	Hallberg J, Dominicus A, de Verdier MG, et al. Interaction between smoking and genetic factors in the development of chronic bronchitis. Am J Respir Crit Care Med, 2008, 177: 486-490.
47.	Lee JH, McDonald MLN, Cho MH, et al. DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease. Respir Res, 2014, 15: 97.
48.	O'Donnell DE, Asron S, Bourbeau J, et al. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease - 2007 update. Can Respir J, 2007, 14 Suppl B(Suppl B): 5B-32B.
49.	Casanova C, Cote C, de Torres JP, et al. Inspiratory-to-total lung capacity ratio predicts mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2005, 171: 591-597.
50.	Buro-Auriemma LJ, Salit J, Hackett NR, et al. Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression. Hum Mol Genet, 2013, 22: 4726-4738.
51.	Leopold PL, O'Mahony MJ, Lian XJ, et al. Smoking is associated with shortened airway cilia. PLoS One, 2009, 4: e8157.
52.	Perotin JM, Polette M, Deslée G, et al. CiliOPD: a ciliopathy-associated COPD endotype. Respir Res, 2021, 22: 74.
53.	Zhang J, Fan W, Wu H, et al. Naringenin attenuated airway cilia structural and functional injury induced by cigarette smoke extract via IL-17 and cAMP pathways. Phytomedicine, 2024, 126: 155053. DOI:10.1016/j.phymed.2023.155053 (2024).
54.	Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin, 2014, 64: 9-29.
55.	Li F, Fang Z, Zhang J, et al. Identification of TRA2B-DNAH5 fusion as a novel oncogenic driver in human lung squamous cell carcinoma. Cell Res, 2016, 26: 1149-1164.

1. Olbrich H, H?ffner K, Kispert A, et al. Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry. Nat Genet, 2002, 30: 143-144.
2. Iba?ez-Tallon I, Heintz N & Omran H. To beat or not to beat: roles of cilia in development and disease. Hum Mol Genet, 2003, 12: R27-R35.
3. Mitchison HM, Valente EM. Motile and non-motile cilia in human pathology: from function to phenotypes. J Pathol, 2017, 241(2): 294-309.
4. Hornef N, Olbrich H, Horvath J, et al. DNAH5 mutations are a common cause of primary ciliary dyskinesia with outer dynein arm defects. Am J Respir Crit Care Med, 2006, 174: 120-126.
5. Oltean A, Schaffer AJ, Bayly PV, et al. Quantifying ciliary dynamics during assembly reveals stepwise waveform maturation in airway cells. Am J Respir Cell Mol Biol, 2018, 59: 511-522.
6. Zheng R, Yang W, Wen Y, et al. Dnah9 mutant mice and organoid models recapitulate the clinical features of patients with PCD and provide an excellent platform for drug screening. Cell Death Dis, 2022, 13: 559.
7. El Zein L, Omran H, Bouvagnet P. Lateralization defects and ciliary dyskinesia: lessons from algae. Trends Genet, 2003, 19(3): 162-167.
8. Emiralio?lu N, Ta?k?ran ZE, Ko?ukcu C, et al. Genotype and phenotype evaluation of patients with primary ciliary dyskinesia: First results from Turkey. Pediatr Pulmonol, 2020, 55: 383-393.
9. 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. BMC Pulm Med, 2021, 21: 263.
10. Chen W, Guo Z, Li M, et al. Next-generation sequencing-based copy number variation analysis in chinese patients with primary ciliary dyskinesia revealed novel DNAH5 copy number variations. Phenomics, 2024, 4: 24-33.
11. Kispert A, Petry M, Olbrich H, et al. Genotype-phenotype correlations in PCD patients carrying DNAH5 mutations. Thorax, 2003, 58: 552-554.
12. Zariwala MA, Knowles MR, Omran H. Genetic defects in ciliary structure and function. Annu Rev Physiol, 2007, 69: 423-450.
13. Yang W, Chen L, Guo J, et al. Multiomics analysis of a DNAH5-mutated PCD organoid model revealed the key role of the TGF-β/BMP and notch pathways in epithelial differentiation and the immune response in DNAH5-mutated patients. Cells, 2022, 11(24): 4013.
14. Chalmers JD, Hill AT. Mechanisms of immune dysfunction and bacterial persistence in non-cystic fibrosis bronchiectasis. Mol Immunol, 2013, 55(1): 27-34.
15. Chen ZG, Li YY, Wang ZN, et al. Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis. J Thorac Dis, 2018, 10(3): 1753-1764.
16. Puchelle E, Zahm JM, Tournier JM, et al. Airway epithelial repair, regeneration, and remodeling after injury in chronic obstructive pulmonary disease. Proc Am Thorac Soc, 2006, 3(8): 726-733.
17. Coraux C, Roux J, Jolly T, et al. Epithelial cell-extracellular matrix interactions and stem cells in airway epithelial regeneration. Proc Am Thorac Soc, 2008, 5(6): 689-694.
18. T?zser J, Earwood R, Kato A, et al. TGF-β signaling regulates the differentiation of motile cilia. Cell Rep, 2015, 11: 1000-1007.
19. Glaser L, Coulter PJ, Shields M, et al. Airway epithelial derived cytokines and chemokines and their role in the immune response to respiratory syncytial virus infection. Pathogens, 2019, 8(3): 106.
20. Yang SC, Chang SH, Hsieh PW, et al. Dipeptide HCH6-1 inhibits neutrophil activation and protects against acute lung injury by blocking FPR1. Free Radic Biol Med, 2017, 106: 254-269.
21. McElvaney OJ, McEvoy NL, McElvaney OF, et al. Characterization of the inflammatory response to severe COVID-19 illness. Am J Respir Crit Care Med, 2020, 202(6): 812-821.
22. Yeleswaram S, Smith P, Burn T, et al. Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment. Clin Immunol, 2020, 218: 108517.
23. Goutaki M, Meier AB, Halbeisen FS, et al. Clinical manifestations in primary ciliary dyskinesia: systematic review and meta-analysis. Eur Respir J, 2016, 48: 1081-1095.
24. Wallmeier J, Nielsen KG, Kuehni CE, et al. Motile ciliopathies. Nat Rev Dis Primers, 2020, 6: 77.
25. Knowles MR, Zariwala M, Leigh M. Primary ciliary dyskinesia. Clin Chest Med, 2016, 37(3): 449-461.
26. Knowles MR, Daniels LA, Davis SD, et al. Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease. Am J Respir Crit Care Med, 2013, 188: 913-922.
27. Djakow J, Svobodová T, Hrach K, et al. Effectiveness of sequencing selected exons of DNAH5 and DNAI1 in diagnosis of primary ciliary dyskinesia. Pediatr Pulmonol, 2012, 47: 864-875.
28. Zhao X, Bian C, Liu K, et al. Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia. Orphanet J Rare Dis, 2021, 16: 293.
29. de Ceuninck van Capelle C, Luo L, Leitner A, et al. Proteomic and structural comparison between cilia from primary ciliary dyskinesia patients with a DNAH5 defect. Front Mol Biosci, 2025, 12: 1593810.
30. Lucas JS, Barbato A, Collins SA, et al. European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Eur Respir J, 2017, 49(1): 1601090.
31. Black HA, de Proce SM, Campos JL, et al. Whole genome sequencing enhances molecular diagnosis of primary ciliary dyskinesia. Pediatr Pulmonol, 2024, 59: 3322-3332.
32. Lai M, Pifferi M, Bush A, et al. Gene editing of DNAH11 restores normal cilia motility in primary ciliary dyskinesia. J Med Genet, 2016, 53(4): 242-249.
33. Chalmers JD, Chang AB, Chotirmall SH, et al. Bronchiectasis. Nat Rev Dis Primers, 2018, 4: 45.
34. Gao YH, Guan WJ, Liu SX, et al. Aetiology of bronchiectasis in adults: a systematic literature review. Respirology, 2016, 21: 1376-1383.
35. Boyton RJ, Altmann DM. Bronchiectasis: current concepts in pathogenesis, immunology, and microbiology. Annu Rev Pathol, 2016, 11: 523-554.
36. Guan WJ, Li JC, Liu F, et al. Next-generation sequencing for identifying genetic mutations in adults with bronchiectasis. J Thorac Dis, 2018, 10: 2618-2630.
37. Morillas HN, Zariwala M, Knowles MR. Genetic causes of bronchiectasis: primary ciliary dyskinesia. Respiration, 2007, 74: 252-263.
38. Zhang RL, Pan CX, Tang CL, Cen LJ, et al. Motile ciliary disorders of the nasal epithelium in adults with bronchiectasis. Chest, 2023, 163(5): 1038-1050.
39. Cloutier MM, Baptist AP, Blake KV, et al. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol, 2020, 146: 1217-1270.
40. Kovacic MB, Myers JM, Wang N, et al. Identification of KIF3A as a novel candidate gene for childhood asthma using RNA expression and population allelic frequencies differences. PLoS One, 2011, 6(8): e23714.
41. Wang T, He C, Wu H, et al. Subtyping children with asthma by clustering analysis of mRNA expression data. Front Genet, 2022, 13: 974936.
42. Shigemasa R, Masuko H, Oshima H, et al. The primary ciliary dyskinesia-related genetic risk score is associated with susceptibility to adult-onset asthma. PLoS One, 2024, 19: e0300000.
43. Corcoran TE, Huber AS, Hill SL, et al. Mucociliary clearance differs in mild asthma by levels of type 2 inflammation. Chest, 2021, 160: 1604-1613.
44. Mak ACY, White M, Eckalbar WL, et al. Whole-genome sequencing of pharmacogenetic drug response in racially diverse children with asthma. Am J Respir Crit Care Med, 2018, 197(12): 1552-1564.
45. Agustí A, Celli BR, Criner GJ, et al. Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary. Eur Respir J, 2023, 61(4): 2300239.
46. Hallberg J, Dominicus A, de Verdier MG, et al. Interaction between smoking and genetic factors in the development of chronic bronchitis. Am J Respir Crit Care Med, 2008, 177: 486-490.
47. Lee JH, McDonald MLN, Cho MH, et al. DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease. Respir Res, 2014, 15: 97.
48. O'Donnell DE, Asron S, Bourbeau J, et al. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease - 2007 update. Can Respir J, 2007, 14 Suppl B(Suppl B): 5B-32B.
49. Casanova C, Cote C, de Torres JP, et al. Inspiratory-to-total lung capacity ratio predicts mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2005, 171: 591-597.
50. Buro-Auriemma LJ, Salit J, Hackett NR, et al. Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression. Hum Mol Genet, 2013, 22: 4726-4738.
51. Leopold PL, O'Mahony MJ, Lian XJ, et al. Smoking is associated with shortened airway cilia. PLoS One, 2009, 4: e8157.
52. Perotin JM, Polette M, Deslée G, et al. CiliOPD: a ciliopathy-associated COPD endotype. Respir Res, 2021, 22: 74.
53. Zhang J, Fan W, Wu H, et al. Naringenin attenuated airway cilia structural and functional injury induced by cigarette smoke extract via IL-17 and cAMP pathways. Phytomedicine, 2024, 126: 155053. DOI:10.1016/j.phymed.2023.155053 (2024).
54. Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin, 2014, 64: 9-29.
55. Li F, Fang Z, Zhang J, et al. Identification of TRA2B-DNAH5 fusion as a novel oncogenic driver in human lung squamous cell carcinoma. Cell Res, 2016, 26: 1149-1164.

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