Hereditary lung diseases and modern possibilities of genetic testing

The European Respiratory Society website gives the following criterion for the disease to be classified as rare (orphan) - the disease occurs in 1 person per 2 000. One of the well-studied rare lung diseases is cystic fibrosis (CF), which is often considered a medical care model for patients with other orphan diseases. However, effective diagnostics and therapies have not yet been developed for many other rare diseases. Moreover, their true prevalence remains unknown because these diseases often go undiagnosed. One of the problems in diagnosing rare diseases is the lack of knowledge among physicians.

The aim of this review is to provide a brief clinical and genetic description of rare hereditary lung diseases and to show modern genetic diagnostics to raise awareness among physicians. Data from 95 articles on hereditary lung diseases were used.

Results. The results of the analysis of lung diseases associated with bronchiectasis, fibrosis, pneumothorax, and hereditary storage diseases are presented. Genetics and diagnostics, including the three-step molecular genetic testing for cystic fibrosis, are considered in detail. The diagnosis has been developed for both neonatal screening and clinical manifestations. The emergence of targeted therapy based on genetic diagnosis makes neonatal screening even more relevant and leads to an increase in life expectancy. A patient registry was established within 10 years. A detailed analysis of the diagnosis of primary ciliary dyskinesia (PCD) is given, taking into account the absence of a single “golden” standard for the diagnosis of PCD. The genetic basis of the most common hereditary diseases and modern possibilities of their diagnosis are discussed, including sequencing of genes responsible for the development of orphan diseases using standard Sanger sequencing methods and next-generation sequencing, and creating multigene panels.

Conclusion. New molecular diagnostic methods will help to understand the nature of orphan lung diseases, study their epidemiology, and develop new diagnostic algorithms. The study of the genetic causes of rare diseases may serve as a basis for the development of targeted therapy.

1. Kutsev S.I., Izhevskaya V.L., Kondratyeva E.I. [Targeted therapy for cystic fibrosis]. Pul’monologiya. 2021; 31 (2): 226-236. DOI: 10.18093/0869-0189-2021-31-2-226-236 (in Russian).

2. Clinical guidelines: Cystic fibrosis]. 2021. Available at: https://mukoviscidoz.org/doc/%D0%9A%D0%A0372.pdf (in Russian).

3. Kondratyeva E.I., Kashirskaya N.Yu., Kapranov N.I., eds. [National consensus “Cystic fibrosis: definition, diagnostic criteria, therapy”]. Moscow: Borges; 2016. Available at: https://mukoviscidoz.org/doc/konsensus/CF_consensus_2017.pdf (in Russian).

4. Castellani C., Cuppens H., Macek M.Jr. et al. Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. J. Cyst. Fibros. 2008; 7 (3): 179-196. DOI: 10.1016/j.jcf.2008.03.009.

5. Richards S., Aziz N., Bale S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015; 17 (5): 405-424. DOI: 10.1038/gim.2015.30.

6. Ivashchenko T.E., Baranov V.S. [Biochemical and molecular genetic basis of the pathogenesis of cystic fibrosis]. St. Petersburg: Intermedika; 2002 (in Russian).

7. Aylamazyan E.K., Baranov V.S., eds. [Prenatal diagnosis of hereditary and congenital diseases]. 2nd Edn. Moscow: MEDpress-inform; 2007. Available at: https://akusher-lib.ru/wp-content/uploads/2018/11/Prenatalnaya-diagnostika-nasledstvennyh-i-vrozhdennyh-boleznej.pdf (in Russian).

8. Harper J.C., Wilton L., Traeger-Synodinos J. et al. The ESHRE PGD Consortium: 10 years of data collection. Hum. Reprod. Update. 2012; 18 (3): 234-247. DOI: 10.1093/humupd/dmr052.

9. Richards S., Aziz N., Bale S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015; 17 (5): 405-424. DOI: 10.1038/gim.2015.30.

10. Shapiro A.J., Zariwala M.A., Ferkol T. et al. Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review. Pediatr. Pulmonol. 2016; 51 (2): 115-132. DOI: 10.1002/ppul.23304.

11. Knowles M.R., Daniels L.A., Davis S.D. et al. Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease. Am. J. Respir. Crit. Care Med. 2013; 188 (8): 913-922. DOI: 10.1164/rccm.201301-0059CI.

12. Miravitlles M., Dirksen A., Ferrarotti I. et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in aj-antitrypsin deficiency. Eur. Respir. J. 2017; 50 (5): 1700610. DOI: 101.1183/13993003.00610-2017.

13. Faughnan M.E., Mager J.J., Hetts S.W. et al. Second International Guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia. Ann. Intern. Med. 2020; 173 (12): 989-1001. DOI: 10.7326/M20-1443.

14. McDonald J., Stevenson D.A. Hereditary hemorrhagic telangiectasia. [Updated: 2021]. In: Adam M.P. Everman D.B., Mirzaa G.M. et al., eds. GeneReviews®. Seattle (WA): University ofWashington; 2000. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1351/

15. Sattler E.C., Steinlein O.K. Birt-Hogg-Dubd syndrome. [Updated: 2020]. In: Adam M.P., Everman D.B., Mirzaa G.M. et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington; 1993-2023. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1522/

16. Boone P.M., Scott R.M., Marciniak S.J. et al. The genetics of pneumothorax. Am. J. Respir. Crit. Care Med. 2019; 199 (11): 1344-1357. DOI: 10.1164/rccm.201807-1212CI.

17. Garcia C.K., Talbert J.L. Pulmonary fibrosis predisposition overview. [Updated: 2022]. In: Adam M.P., Everman D.B., Mirzaa G.M. et al., eds. GeneReviews® [Internet]. Seattle (WA): University ofWashington; 1993-2023. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1230/

18. Kropski J.A., Young L.R., Cogan J.D. et al. Genetic evaluation and testing of patients and families with idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 2017; 195 (11): 1423-1428. DOI: 10.1164/rccm.201609-1820PP.

19. Northrup H., Koenig M.K., Pearson D.A., Au K.S. Tuberous sclerosis complex. [Updated: 2021]. In: Adam M.P., Everman D.B., Mirzaa G.M. et al., eds. GeneReviews® [Internet]. Seattle (WA): University ofWashington; 1993-2023. Available at: https://www.ncbi. nlm.nih.gov/books/NBK1220/

20. Huizing M., Malicdan M.C.V., Gochuico B.R., Gahl W.A. Her-mansky-Pudlak syndrome. [Updated: 2021]. In: Adam M.P., Everman D.B., Mirzaa G.M. et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington; 1993-2023. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1287/

21. Gatti R., Perlman S. Ataxia-telangiectasia. [Updated: 2016]. In: Adam M.P., Everman D.B., Mirzaa G.M. et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington; 1993-2023. Available at: https://www.ncbi.nlm.nih.gov/books/NBK26468/

22. Smith C.E., Berglof A. X-linked agammaglobulinemia. [Updated: 2016]. In: Adam M.P., Everman D.B., Mirzaa G.M. et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington; 1993-2023. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1453/

23. Allenspach E.J., Rawlings D.J., Petrovic A. et al. X-linked severe combined immunodeficiency. [Updated: 2021]. In: Adam M.P., Everman D.B., Mirzaa G.M. et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington; 1993-2023. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1410/

24. Shearer W.T., Dunn E., Notarangelo L.D. et al. Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the primary immune deficiency treatment consortium experience. J. Allergy Clin. Immunol. 2014; 133 (4): 1092-1098. DOI: 10.1016/j.jaci.2013.09.044.

25. Mizernitskiy Yu.L., Tsaregorodtsev A.D., eds. [Pulmonology of childhood: problems and solutions]. Issue 12. Moscow: Medpraktika-M; 2012. Available at: https://pedklin.ru/images/images/uploads/pages/v12.pdf (in Russian).

26. Kobrinskiy B.A., Po-dol’naya M.A., Bogorad A.E. [Register of rare chronic lung diseases in children]. Vrach i informatsionnye tekhnologii. 2015; (3): 64-69. Available at: https://cyberleninka.ru/article/n/registr-redkih-hronicheskih-zabolevaniy-legkih-u-detey?ysclid=lewvn975rj382571824 (in Russian).

27. Капранов Н.И., Каширская Н.Ю., ред. Муковисцидоз. М.: Медпрактика-М; 2014. / Kapranov N.I., Kashirskaya N.Yu., eds. [Cystic fibrosis]. Moscow: Medpraktika-M; 2014 (in Russian).

28. Kashirskaya N.Yu., Kapranov N.I., Kondrat’eva E.I., eds. [Cystic fibrosis]. 2nd Edn. Moscow: Medpraktika-M; 2021. Available at: http://www.medpractika.ru/books/new/?id=316 (in Russian).

29. Petrova N, Balinova N., Marakhonov A. et al. Ethnic differences in the frequency of CFTR gene mutations in populations of the European and North Caucasian part of the Russian Federation. Front. Genet. 2021; 12: 678374. DOI: 10.3389/fgene.2021.678374.

30. Il’enkova N.A., Chikunov V.V., Kondratyeva E.I. [Features of spectrum of pathogenic genetic variants of the CFTR gene in patients with cystic fibrosis from Krasnoyarsk territory]. Meditsinskiy vestnik Severnogo Kavkaza. 2020; 15 (2): 178-181. DOI: 10.14300/mnnc.2020.15043 (in Russian).

31. Shadrina V.V., Kondrat’eva E.I., Furman E.G. et al. [Basic clinico-laboratory and genetic characteristic of patients with mucoviscidosis living in Perm krai, other regions of Privolzhsky federal district and Central federal district of Russia]. Permskiy meditsinskiy zhurnal. 2020; 37 (1): 48-62. DOI: 10.17816/pmj37148-62 (in Russian).

32. Kondratyeva E.I., Petrova N.V., Voronkova A.Yu. et al. [Variety of large rearrangements in the CFTR gene in Russian patients with Cystic Fibrosis]. Meditsinskayagenetika. 2020; 19 (2): 28-34. DOI: 10.25557/2073-7998.2020.02.28-34 (in Russian).

33. Petrova N.V., Marakhonov A.Yu., Vasil’eva T.A. et al. [Characteristics of the mutation spectrum identified by comprehensive investigation of the CFTR gene in the Russian patients]. Al’manakh klinicheskoy meditsiny. 2019; 47 (1): 38-46. DOI: 10.18786/2072-0505-2019-47-004 (in Russian).

34. Kondratyeva E.I., Krasovskiy S.A., Starinova M.A. et al. [Register of patients with cystic fibrosis in the Russian Federation. 2020]. Moscow: Medpraktika-M; 2022. Available at: https://api.med-gen.ru/site/assets/files/51107/site_registre_2020.pdf (in Russian).

35. Castellani C., Duff A.J.A., Bell S.C. et al. ECFS best practice guidelines: the 2018 revision. J. Cyst. Fibros. 2018; 17 (2): 153-178. DOI: 10.1016/j.jcf.2018.02.006.

36. Kondratyeva E.I., Amelina E.L., Chernukha M.Yu. [Review of clinical guidelines “Cystic fibrosis”, 2020]. Pul’monologiya. 2021; 31 (2): 135-146. DOI: 10.18093/0869-0189-2021-31-2-135-146 (in Russian).

37. Lucas J.S., Barbato A., Collins S.A. et al. European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Eur. Respir. J. 2017; 49 (1): 1601090. DOI: 10.1183/13993003.01090-2016.

38. Lieberman J., Winter B., Sastre A. Alphaj-antitrypsin Pi-types in 965 COPD patients. Chest. 1986; 89 (3): 370-373. DOI: 10.1378/chest.89.3.370.

39. Zhurkova N.V., Kondakova O.B., Strokova T.V. et al. [dj-Antitrypsin deficiency in children with liver pathology]. Pediatriya. 2008; 87 (3): 138-141. Available at: https://cyberleninka.ru/article/n/nedostatochnost-1-antitripsina-u-detey-s-patologiey-pecheni (in Russian).

40. Stoller J.K., Hupertz V., Aboussouan L.S. Alpha-1 antitrypsin deficiency. [Updated: 2020]. In: Adam M.P., Everman D.B., Mir-zaa G.M. et al., eds. GeneReviews® [Internet]. Seattle (WA): University ofWashington; 1993-2023. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1519/

41. Diagnosis and treatment of pulmonarydisease in dj-antitrypsin deficiency: a statement of European Respiratory Society]. Pul’monologiya. 2018; 28 (3): 273-295. DOI: 10.18093/0869-0189-2018-28-3-273-295 (in Russian).

42. Strakhov S.N., Rozinova N.N., Sokolova L.V. et al. [Osler-Ran-du-Weber disease with lung involvement in children]. Rossiyskiy vestnik perinatologii i pediatrii. 1994; 39 (4): 31-33 (in Russian).

43. Kuhnel T., Wirsching K., Wohlgemuth W. et al. Hereditary hemorrhagic telangiectasia. Otolaryngol. Clin. North Am. 2018; 51 (1): 237-254. DOI: 10.1016/j.otc.2017.09.017.

44. van Gent M.W., Post M.C., Snijder R.J. et al. Real prevalence of pulmonary right-to-left shunt according to genotype in patients with hereditary hemorrhagic telangiectasia: a transthoracic contrast echocardiography study. Chest. 2010; 138 (4): 833-839. DOI: 10.1378/chest.09-1849.

45. Blivet S., Cobarzan D., Beauchet A. et al. Impact of pulmonary arteriovenous malformations on respiratory-related quality of life in patients with hereditary haemorrhagic telangiectasia. PLoS One. 2014; 9 (3): e90937. DOI: 10.1371/journal.pone.0090937.

46. Shovlin C.L., Chamali B., Santhirapala V. et al. Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets. PLoS One. 2014; 9 (2): e88812. DOI: 10.1371/journal.pone.0088812.

47. Al-Samkari H. Hereditary hemorrhagic telangiectasia: systemic therapies, guidelines, and an evolving standard of care. Blood. 2021; 137 (7): 888-895. DOI: 10.1182/blood.2020008739.

48. Menko F.H., van Steensel M.A., Giraud S. et al. Birt-Hogg-Dubd syndrome: diagnosis and management. Lancet Oncol. 2009; 10 (12): 1199-1206. DOI: 10.1016/S1470-2045(09)70188-3.

49. Gunji Y., Akiyoshi T., Sato T. et al. Mutations of the Birt-Hogg-Dube gene in patients with multiple lung cysts and recurrent pneumothorax. J. Med. Genet. 2007; 44 (9): 588-593. DOI: 10.1136/jmg.2007.049874.

50. Schmidt L.S., Nickerson M.L., Warren M.B. et al. Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubd syndrome. Am. J. Hum. Genet. 2005; 76 (6): 1023-1033. DOI: 10.1086/430842.

51. Graham R.B., Nolasko M., Peterlin B., Garcia C.K. Nonsense mutations in folliculin presenting as isolated familial spontaneous pneumothorax in adults. Am. J. Respir. Crit. Care Med. 2005; 172 (1): 39-44. DOI: 10.1164/rccm.200501-143OC.

52. Toro J.R., Wei M.H., Glenn G.M. et al. BHD mutations, clinial and molecular genetic investigations of Birt-Hogg-Dubd syndrome: a new series of 50 families and a review of published reports. J. Med. Genet. 2008; 45 (6): 321-331. DOI: 10.1136/jmg.2007.054304.

53. Misago N., Joh K., Yatsuki H. et al. A BHD germline mutation identified in an Asian family with Birt-Hogg-Dubd syndrome. Acta Derm. Venereol. 2008; 88 (4): 423-425. DOI: 10.2340/00015555-0439.

54. Frohlich B.A., Zeitz C., Mdtyds G. et al. Novel mutations in the folliculin gene associated with spontaneous pneumothorax. Eur. Respir. J. 2008; 32 (5): 1316-1320. DOI: 10.1183/09031936.00132707.

55. Leter E.M., Koopmans A.K., Gille J.J. et al. Birt-Hogg-Dubd syndrome: clinical and genetic studies of 20 families. J. Invest. Dermatol. 2008; 128 (1): 45-49. DOI: 10.1038/sj.jid.5700959.

56. Woodward E.R., Ricketts C., Killick P. et al. Familial non-VHL clear cell (conventional) renal cell carcinoma: clinical features, segregation analysis, and mutation analysis of FLCN. Clin. Cancer Res. 2008; 14 (18): 5925-5930. DOI: 10.1158/1078-0432.CCR-08-0608.

57. Butnor K.J., Guinee D.G. Jr. Pleuropulmonary pathology of Birt-Hogg-Dubd syndrome. Am. J. Surg. Pathol. 2006; 30 (3): 395-399. DOI: 10.1097/01.pas.0000183571.17011.06.

58. Ayo D.S., Aughenbaugh G.L., Yi E.S. et al. Cystic lung disease in Birt-Hogg-Dube syndrome. Chest. 2007; 132 (2): 679-684. DOI: 10.1378/chest.07-0042.

59. Graham R.B., Nolasco M., Peterlin B., Garcia C.K. Nonsense mutations in folliculin presenting as isolated familial spontaneous pneumothorax in adults. Am. J. Respir. Crit. Care Med. 2005; 172 (1): 39-44. DOI: 10.1164/rccm.200501-143OC.

60. Furuya M., Nakatani Y. Birt-Hogg-Dube syndrome: clinicopath-ological features of the lung. J. Clin. Pathol. 2013; 66 (3): 178-186. DOI: 10.1136/jclinpath-2012-201200.

61. Zbar B., Alvord W.G., Glenn G. et al. Risk of renal and colonic neoplasms and spontaneous pneumothorax in the Birt-Hogg-Dubd syndrome. Cancer Epidemiol. Biomarkers Prev. 2002; 11 (4): 393-400. Available at: https://aacrjournals.org/cebp/article/11/4/393/166608/Risk-of-Renal-and-Colonic-Neoplasms-and

62. Toro J.R., Pautler S.E., Stewart L. et al. Lung cysts, spontaneous pneumothorax, and genetic associations in 89 families with Birt-Hogg-Dubd syndrome. Am. J. Respir. Crit. Care Med. 2007; 175 (10): 1044-1053. DOI: 10.1164/rccm.200610-1483OC.

63. Davis A.M, Wensley D.F, Phelan P.D. Spontaneous pneumothorax in paediatric patients. Respir. Med. 1993; 87 (7): 531-534. DOI: 10.1016/0954-6111(93)90009-o.

64. Berlin R. Familial occurrence of pneumothorax simplex. Acta Med. Scand. 1950; 137 (4): 268-275. DOI: 10.1111/j.0954-6820.1950.tb11378.x.

65. Boyd D.H. Familial spontaneous pneumothorax. Scott. Med. J. 1957; 2 (5): 220-221. DOI: 10.1177/003693305700200506.

66. Ren H.Z, Zhu C.C, Yang C. et al. Mutation analysis of the FLCN gene in Chinese patients with sporadic and familial isolated primary spontaneous pneumothorax. Clin. Genet. 2008; 74 (2): 178-183. DOI: 10.1111/j.1399-0004.2008.01030.x.

67. Bourneville D.M. Sclerose tubereuse des circonvolutions cerebrales: idiotie et epilepsie hemiplegique. Arch. Neurol. (Paris). 1880; 1: 81-91.

68. Orlova K.A., Crino P.B. The tuberous sclerosis complex. Ann. N.Y. Acad. Sci. 2010; 1184: 87-105. DOI: 10.1111/j.1749-6632.2009.05117.x.

69. Crino P.B., Nathanson K.L., Henske E.P. The tuberous sclerosis complex. N. Engl. J. Med. 2006; 355 (13): 1345-1356. DOI: 10.1056/NEJMra055323.

70. Franz D.N., Brody A., Meyer C. et al. Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyo-matosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis. Am. J. Respir. Crit. Care Med. 2001; 164: 661-668. DOI: 10.1164/ajrccm.164.4.2011025.

71. Costello L.C., Hartman T.E., Ryu J.H. High frequency of pulmonary lymphangioleiomyomatosis in women with tuberous sclerosis complex. Mayo Clin. Proc. 2000; 75 (6): 591-594. DOI: 10.4065/75.6.591.

72. Bissler J.J., McCormack F.X., Young L.R. et al. Sirolimus for an-giomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N. Engl. J. Med. 2008; 358 (2): 140-151. DOI: 10.1056/NEJMoa063564.

73. Goldberg H.J., Harari S., Cottin V. et al. Everolimus for the treatment of lymphangioleiomyomatosis: a phase II study. Eur. Respir. J. 2015; 46 (3): 783-794. DOI: 10.1183/09031936.00210714.

74. Boytsova E.V., Ovsyannikov D.Yu., Belyashova M.A. [Interstitial lung disease in children]. Vestnik sovremennoy klinicheskoy meditsiny. 2014; (6): 71-76. Available at: http://vskmjournal.org/images/Files/Issues_Archive/2014/Issue_6/VSKM_2014_N_6_p71-76.pdf (in Russian).

75. Avdeev S. N. [Idiopatic pulmonary fibrosis: а new paradigm]. Terapevticheskiy arkhiv. 2017; 89 (1): 112-122. DOI: 10.17116/terarkh2017891112-122 (in Russian).

76. Avdeev S.N. [Hypersensitivity pneumonitis]. Pul’monologiya. 2021; 31 (1): 88-99. DOI: 10.18093/0869-0189-2021-31-1-88-99

77. Russian Respiratory Society [Clinical guidelines: Idiopathic pulmonary fibrosis]. 2021. Available at: https://spulmo.ru/upload/kr/ILF_2021.pdf (in Russian).

78. Vancheri C., Failla M., Crimi N., Raghu G. Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology. Eur. Respir. J. 2010; 35 (3): 496-504. DOI: 10.1183/09031936.00077309.

79. Newton C.A., Molyneaux P.L., Oldham J.M. Clinical genetics in interstitial lung disease. Front. Med. (Lausanne). 2018; 5: 116. DOI: 10.3389/fmed.2018.00116.

80. Martinez F.J., de Andrade J.A., Anstrom K.J. et al. Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis. N. Engl. J. Med. 2014; 370 (22): 2093-2101. DOI: 10.1056/NEJMoa1401739.

81. Raghu G., Anstrom K.J., King T.E. Jr et al. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N. Engl. J. Med. 2012; 366 (21): 1968-1977. DOI: 10.1056/NEJMoa1113354.

82. Oldham J.M., Ma S.F., Martinez F.J. et al. TOLLIP, MUC5B, and the response to N-acetylcysteine among Individuals with idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 2015; 192 (12): 1475-1482. DOI: 10.1164/rccm.201505-1010OC.

83. Raghu G., Remy-Jardin M., Richeldi L. et al. Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: an official ATS/ERS/JRS/ALAT clinical practice guideline. Am. J. Respir. Crit. Care Med. 2022; 205 (9): e18-47. DOI: 10.1164/rc-cm.202202-0399ST.

84. Chuchalin A.G., Avdeev S.N., Aisanov Z.R. et al. [Diagnosis and treatment of idiopathic pulmonary fibrosis. Federal guidelines]. Pul’monologiya. 2016; 26 (4): 399-419. DOI: 10.18093/0869-0189-2016-26-4-399-419 (in Russian).

85. Huizing M., Malicdan M.C.V., Wang J.A. et al. Hermansky-Pudlak syndrome: mutation update. Hum. Mutat. 2020; 41: 543-580. DOI: 10.1002/humu.23968.

86. El-Chemaly S., Young L.R. Hermansky-Pudlak syndrome. Clin. Chest Med. 2016; 37 (3): 505-511. DOI: 10.1016/j.ccm.2016.04.012.

87. Vicary G.W., Vergne Y., Santiago-Cornier A. et al. Pulmonary fibrosis in Hermansky-Pudlak syndrome. Ann. Am. Thorac. Soc. 2016; 13 (10): 1839-1846. DOI: 10.1513/AnnalsATS.201603-186FR.

88. Harada T., Ishimatsu Y., Nakashima S. et al. An autopsy case of Hermansky-Pudlak syndrome: a case report and review of the literature on treatment. Intern. Med. 2014; 53 (23): 2705-2709. DOI: 10.2169/internalmedicine.53.2239.

89. Bin Saeedan M., Faheem Mohammed S., Mohammed T.L. Hermansky-Pudlak syndrome: high-resolution computed tomography findings and literature review. Curr. Probl. Diagn. Radiol. 2015; 44 (4): 383-385. DOI: 10.1067/j.cpradiol.2015.01.003.

90. O’Brien K.J., Introne W.J., Akal O. et al. Prolonged treatment with open-label pirfenidone in Hermansky-Pudlak syndrome pulmonary fibrosis. Mol. Genet. Metab. 2018; 125 (1-2): 168-173. DOI: 10.1016/j.ymgme.2018.07.012.

91. El-Chemaly S., O’Brien K.J., Nathan S.D. et al. Clinical management and outcomes of patients with Hermansky-Pudlak syndrome pulmonary fibrosis evaluated for lung transplantation. PLoS One. 2018; 13 (3): e0194193. DOI: 10.1371/journal.pone.0194193.

92. Avdeev S.N., Aisanov Z.R., Belevskiy A.S. et al. [Federal clinical guidelines on diagnosis and treatment of idiopathic pulmonary fibrosis]. Pul’monologiya. 2022; 32 (3): 473-495. DOI: 10.18093/0869-0189-2022-32-3-473-495 (in Russian).

93. Shamsutdinova N.G., Nurullina G.I., Il’inskiy V.I. et al. [Rare lung diseases associated with accumulation]. Prakticheskaya meditsina. 2018; 16 (7, Pt 2): 109-112. Available at: https://cyberleninka.ru/article/n/redkie-zabolevaniya-legkih-svyazannye-s-nakopleniem (in Russian).

94. Bourke S.J. Interstitial lung disease: progress and problems. Postgrad. Med. J. 2006; 82 (970): 494-499. DOI: 10.1136/pgmj.2006.046417.

95. Castellana G., Castellana G., Gentile M. et al. Pulmonary alveolar microlithiasis: review of the 1022 cases reported worldwide. Eur. Respir. Rev. 2015; 24 (138): 607-620. DOI: 10.1183/16000617.0036-2015.

96. Saito A., McCormack F.X. Pulmonary alveolar microlithiasis. Clin. Chest Med. 2016; 37 (3): 441-448. DOI: 10.1016/j.ccm.2016.04.007.

97. Ovsyannikov D.Yu., Boytsova U.V., Zhestkova M.A. et al. [Neonatal pulmonology]. Moscow; 2022. Available at: https://kingmed.info/media/book/5/4700.pdf (in Russian).

98. Cole F.S, Hamvas A., Rubinstein P. et al. Population-based estimates of surfactant protein B deficiency. Pediatrics. 2000; 105 (3, Pt 1): 538-541. DOI: 10.1542/peds.105.3.538.

99. Hamvas A., Trusgnich M., Brice H. et al. Population-based screening for rare mutations: high-throughput DNA extraction and molecular amplification from Guthrie cards. Pediatr. Res. 2001; 50 (5): 666-668. DOI: 10.1203/00006450-200111000-00021.

100. Ovsyannikov D. Yu., Belyashova M.A., Krushel’nitskiy A.A. [Congenital deficiency of surfactant proteins]. Neonatologiya: novosti, mneniya, obuchenie. 2014; (1 (3)): 80-90. Available at: https://cyberleninka.ru/article/n/vrozhdennyy-defitsit-belkov-surfaktanta/viewer (in Russian).

101. Floros J., Fan R. Surfactant protein A and B genetic variants and respiratory distress syndrome, allele interactions. Biol. Neonate. 2001; 80 (Suppl. 1): 22-25. DOI: 10.1159/000047173.

102. Kurland G., Deterding R.R., Hagood J.S. et al. An official American Thoracic Society clinical practice guideline: Classification, evaluation, and management of childhood interstitial lung disease in infancy. Am. J. Respir. Crit. Care Med. 2013; 188 (3): 376-394. DOI: 10.1164/rccm.201305-0923ST.

103. Tangye S.G., Al-Herz W., Bousfiha A. et al. Human inborn errors of immunity: 2019 update on the classification from the International Union of Immunological Societies Expert Committee. J. Clin. Immunol. 2020; 40 (1): 24-64. DOI: m.m07/s10875-019-00737-x.

104. Chinn I.K., Chan A.Y., Chen K. et al. Diagnostic interpretation of genetic studies in patients with primary immunodeficiency diseases: A working group report of the Primary Immunodeficiency Diseases Committee of the American Academy of Allergy, Asthma and Immunology. J. Allergy Clin. Immunol. 2020; 145 (1): 46-69. DOI: 10.1016/j.jaci.2019.09.009.

105. Leonardi L., Rivalta B., Cancrini C. et al. Update in primary immunodeficiencies. Acta Biomed. 2020; 91 (11, Suppl.): e2020010. DOI: 10.23750/abm.v91i11-S.10314.

106. Swift M., Morrell D., Cromartie E. et al. The incidence and gene frequency of ataxia-telangiectasia in the United States. Am. J. Hum. Genet. 1986; 39 (5): 573-583. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1684065/

107. Bott L., Lebreton J., Thumerelle C. et al. Lung disease in ataxia-telangiectasia. Acta Paediatr. 2007; 96 (7): 1021-1024. DOI: 10.1111/j.1651-2227.2007.00338.x.

108. Nowak-Wegrzyn A., Crawford T.O., Winkelstein J.A. et al. Immunodeficiency and infections in ataxia-telangiectasia. J. Pediatr. 2004; 144 (4): 505-511. DOI: 10.1016/j.jpeds.2003.12.046.

109. Schroeder S.A., Swift M., Sandoval C., Langston C. Interstitial lung disease in patients with ataxia-telangiectasia. Pediatr. Pulmonol. 2005; 39 (6): 537-543. DOI: 10.1002/ppul.20209.

110. Ryzhkova O.P., Kardymon O.L., Prokhorchuk E.B. et al. [Mass gain manual for human DNA mass gain analytical sequencing (MPS) mass gain (2018 Revision, Version 2)]. Meditsinskayagenetika. 2019; 18 (2): 3-23. DOI: 10.25557/2073-7998.2019.02.3-23 (in Russian).

111. Anikaev A.Yu., Lomonosov A.M. [Clinical applications of next-generation sequencing (NGS)]. Laboratornaya sluzhba. 2014; 3 (1): 32-36. Available at: https://www.mediasphera.ru/issues/labo-ratornaya-sluzhba/2014/1/032305-2198201415 (in Russian).

112. Richards S., Aziz N., Bale S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 2015; 17 (5): 405-424. DOI: 10.1038/gim.2015.30.

113. Voinova V.Yu., Nikolaeva E.A., Shcherbakova N.V., Yablonskaya M.I. [High-performance DNA sequencing to identify genetically determined diseases in pediatric practice]. Rossiyskiy vestnikperinatologii ipediatrii. 2019; 64 (1): 103-109. DOI: 10.21508/1027-4065-2019-64-1-103-109 (in Russian).