Skip to main content
SpringerLink
Log in

Differential Diagnosis of Diffuse Pulmonary Disorders Using Genetics

  • Chapter
  • First Online:
Book cover Precision in Pulmonary, Critical Care, and Sleep Medicine

Part of the book series: Respiratory Medicine ((RM))

  • 755 Accesses

Abstract

Through the past several decades, there has been substantial progress in defining the role of genetic factors in risk for a variety of pulmonary diseases. This progress has advanced understanding of the pathobiology of chronic lung diseases, laying the groundwork for the first genetically informed precision therapies for lung disease. With rapid growth of available genetic tests for patients with pulmonary diseases, there is an urgent need to precisely define the role of genetic evaluation and testing in the clinical care of patients with pulmonary diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA, et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet. 2011;12(11):745–55.

    Article  CAS  PubMed  Google Scholar 

  2. Rabbani B, Mahdieh N, Hosomichi K, Nakaoka H, Inoue I. Next-generation sequencing: impact of exome sequencing in characterizing Mendelian disorders. J Hum Genet. 2012;57(10):621–32.

    Article  CAS  PubMed  Google Scholar 

  3. Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, et al. Clinical whole-exome sequencing for the diagnosis of Mendelian disorders. N Engl J Med. 2013;369(16):1502–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Richards 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):405–24.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kropski JA, Young LR, Cogan JD, Mitchell DB, Lancaster LH, Worrell JA, et al. Genetic evaluation and testing of patients and families with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2017;195(11):1423–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, et al. European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants–2013 update. Neonatology. 2013;103(4):353–68.

    Article  PubMed  Google Scholar 

  7. Nogee LM. Genetic causes of surfactant protein abnormalities. Curr Opin Pediatr. 2019;31:330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nogee LM, Garnier G, Dietz HC, Singer L, Murphy AM, deMello DE, et al. A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds. J Clin Invest. 1994;93(4):1860–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Vorbroker DK, Profitt SA, Nogee LM, Whitsett JA. Aberrant processing of surfactant protein C in hereditary SP-B deficiency. Am J Phys. 1995;268(4 Pt 1):L647–56.

    CAS  Google Scholar 

  10. Nogee LM, Dunbar AE 3rd, Wert SE, Askin F, Hamvas A, Whitsett JA. A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med. 2001;344(8):573–9.

    Article  CAS  PubMed  Google Scholar 

  11. Beers MF, Hawkins A, Maguire JA, Kotorashvili A, Zhao M, Newitt JL, et al. A nonaggregating surfactant protein C mutant is misdirected to early endosomes and disrupts phospholipid recycling. Traffic. 2011;12(9):1196–210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lawson WE, Cheng DS, Degryse AL, Tanjore H, Polosukhin VV, Xu XC, et al. Endoplasmic reticulum stress enhances fibrotic remodeling in the lungs. Proc Natl Acad Sci U S A. 2011;108(26):10562–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Maguire JA, Mulugeta S, Beers MF. Endoplasmic reticulum stress induced by surfactant protein C BRICHOS mutants promotes proinflammatory signaling by epithelial cells. Am J Respir Cell Mol Biol. 2011;44(3):404–14.

    Article  CAS  PubMed  Google Scholar 

  14. Mulugeta S, Maguire JA, Newitt JL, Russo SJ, Kotorashvili A, Beers MF. Misfolded BRICHOS SP-C mutant proteins induce apoptosis via caspase-4- and cytochrome c-related mechanisms. Am J Physiol Lung Cell Mol Physiol. 2007;293(3):L720–9.

    Article  CAS  PubMed  Google Scholar 

  15. Mulugeta S, Nguyen V, Russo SJ, Muniswamy M, Beers MF. A surfactant protein C precursor protein BRICHOS domain mutation causes endoplasmic reticulum stress, proteasome dysfunction, and caspase 3 activation. Am J Respir Cell Mol Biol. 2005;32(6):521–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang WJ, Mulugeta S, Russo SJ, Beers MF. Deletion of exon 4 from human surfactant protein C results in aggresome formation and generation of a dominant negative. J Cell Sci. 2003;116(Pt 4):683–92.

    Article  CAS  PubMed  Google Scholar 

  17. Thomas AQ, Lane K, Phillips J 3rd, Prince M, Markin C, Speer M, et al. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Am J Respir Crit Care Med. 2002;165(9):1322–8.

    Article  PubMed  Google Scholar 

  18. Crossno PF, Polosukhin VV, Blackwell TS, Johnson JE, Markin C, Moore PE, et al. Identification of early interstitial lung disease in an individual with genetic variations in ABCA3 and SFTPC. Chest. 2010;137(4):969–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bullard JE, Wert SE, Nogee LM. ABCA3 deficiency: neonatal respiratory failure and interstitial lung disease. Semin Perinatol. 2006;30(6):327–34.

    Article  PubMed  Google Scholar 

  20. Bullard JE, Wert SE, Whitsett JA, Dean M, Nogee LM. ABCA3 mutations associated with pediatric interstitial lung disease. Am J Respir Crit Care Med. 2005;172(8):1026–31.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Shulenin S, Nogee LM, Annilo T, Wert SE, Whitsett JA, Dean M. ABCA3 gene mutations in newborns with fatal surfactant deficiency. N Engl J Med. 2004;350(13):1296–303.

    Article  CAS  PubMed  Google Scholar 

  22. Wambach JA, Casey AM, Fishman MP, Wegner DJ, Wert SE, Cole FS, et al. Genotype-phenotype correlations for infants and children with ABCA3 deficiency. Am J Respir Crit Care Med. 2014;189(12):1538–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wambach JA, Yang P, Wegner DJ, Heins HB, Kaliberova LN, Kaliberov SA, et al. Functional characterization of ATP-binding cassette transporter A3 mutations from infants with respiratory distress syndrome. Am J Respir Cell Mol Biol. 2016;55(5):716–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Young LR, Nogee LM, Barnett B, Panos RJ, Colby TV, Deutsch GH. Usual interstitial pneumonia in an adolescent with ABCA3 mutations. Chest. 2008;134(1):192–5.

    Article  CAS  PubMed  Google Scholar 

  25. Doyle DA, Gonzalez I, Thomas B, Scavina M. Autosomal dominant transmission of congenital hypothyroidism, neonatal respiratory distress, and ataxia caused by a mutation of NKX2-1. J Pediatr. 2004;145(2):190–3.

    Article  CAS  PubMed  Google Scholar 

  26. Guillot L, Carre A, Szinnai G, Castanet M, Tron E, Jaubert F, et al. NKX2-1 mutations leading to surfactant protein promoter dysregulation cause interstitial lung disease in “Brain-Lung-Thyroid Syndrome”. Hum Mutat. 2010;31(2):E1146–62.

    Article  PubMed  Google Scholar 

  27. Young LR, Deutsch GH, Bokulic RE, Brody AS, Nogee LM. A mutation in TTF1/NKX2.1 is associated with familial neuroendocrine cell hyperplasia of infancy. Chest. 2013;144(4):1199–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Reiter J, Szafranski P, Breuer O, Perles Z, Dagan T, Stankiewicz P, et al. Variable phenotypic presentation of a novel FOXF1 missense mutation in a single family. Pediatr Pulmonol. 2016;51(9):921–7.

    Article  PubMed  Google Scholar 

  29. Sen P, Gerychova R, Janku P, Jezova M, Valaskova I, Navarro C, et al. A familial case of alveolar capillary dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human. Eur J Hum Genet. 2013;21(4):474–7.

    Article  CAS  PubMed  Google Scholar 

  30. Luk HM, Tang T, Choy KW, Tong MF, Wong OK, Lo FM. Maternal somatic mosaicism of FOXF1 mutation causes recurrent alveolar capillary dysplasia with misalignment of pulmonary veins in siblings. Am J Med Genet A. 2016;170(7):1942–4.

    Article  PubMed  Google Scholar 

  31. Watkin LB, Jessen B, Wiszniewski W, Vece TJ, Jan M, Sha Y, et al. COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis. Nat Genet. 2015;47:654–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Tsui JL, Estrada OA, Deng Z, Wang KM, Law CS, Elicker BM, et al. Analysis of pulmonary features and treatment approaches in the COPA syndrome. ERJ Open Res. 2018;4(2):00017–2018. https://doi.org/10.1183/23120541.00017-2018.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Sanchez GAM, et al. Activated STING in a vascular and pulmonary syndrome. N Engl J Med. 2014;371(6):507–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Trapnell BC, Nakata K, Bonella F, Campo I, Griese M, Hamilton J, et al. Pulmonary alveolar proteinosis. Nat Rev Dis Primers. 2019;5(1):16.

    Article  PubMed  Google Scholar 

  35. Dranoff G, Crawford AD, Sadelain M, Ream B, Rashid A, Bronson RT, et al. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Science. 1994;264(5159):713–6.

    Article  CAS  PubMed  Google Scholar 

  36. McCarthy C, Avetisyan R, Carey BC, Chalk C, Trapnell BC. Prevalence and healthcare burden of pulmonary alveolar proteinosis. Orphanet J Rare Dis. 2018;13(1):129.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Dirksen U, Nishinakamura R, Groneck P, Hattenhorst U, Nogee L, Murray R, et al. Human pulmonary alveolar proteinosis associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta chain expression. J Clin Invest. 1997;100(9):2211–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Suzuki T, Sakagami T, Rubin BK, Nogee LM, Wood RE, Zimmerman SL, et al. Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA. J Exp Med. 2008;205(12):2703–10.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Trapnell BC, Whitsett JA, Nakata K. Pulmonary alveolar proteinosis. N Engl J Med. 2003;349(26):2527–39.

    Article  CAS  PubMed  Google Scholar 

  40. Borsani G, Bassi MT, Sperandeo MP, De Grandi A, Buoninconti A, Riboni M, et al. SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance. Nat Genet. 1999;21(3):297–301.

    Article  CAS  PubMed  Google Scholar 

  41. Hadchouel A, Wieland T, Griese M, Baruffini E, Lorenz-Depiereux B, Enaud L, et al. Biallelic mutations of methionyl-tRNA synthetase cause a specific type of pulmonary alveolar proteinosis prevalent on reunion island. Am J Hum Genet. 2015;96(5):826–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Griese M, Zarbock R, Costabel U, Hildebrandt J, Theegarten D, Albert M, et al. GATA2 deficiency in children and adults with severe pulmonary alveolar proteinosis and hematologic disorders. BMC Pulm Med. 2015;15:87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Spinner MA, Sanchez LA, Hsu AP, Shaw PA, Zerbe CS, Calvo KR, et al. GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. Blood. 2014;123(6):809–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Fremond ML, Hadchouel A, Schweitzer C, Berteloot L, Bruneau J, Bonnet C, et al. Successful haematopoietic stem cell transplantation in a case of pulmonary alveolar proteinosis due to GM-CSF receptor deficiency. Thorax. 2018;73(6):590–2.

    Article  PubMed  Google Scholar 

  45. Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67–119.

    Article  PubMed  Google Scholar 

  46. Chew JD, Loyd JE, Austin ED. Genetics of pulmonary arterial hypertension. Semin Respir Crit Care Med. 2017;38(5):585–95.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Evans JD, Girerd B, Montani D, Wang XJ, Galie N, Austin ED, et al. BMPR2 mutations and survival in pulmonary arterial hypertension: an individual participant data meta-analysis. Lancet Respir Med. 2016;4(2):129–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Machado RD, Southgate L, Eichstaedt CA, Aldred MA, Austin ED, Best DH, et al. Pulmonary arterial hypertension: a current perspective on established and emerging molecular genetic defects. Hum Mutat. 2015;36(12):1113–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Soubrier F, Chung WK, Machado R, Grunig E, Aldred M, Geraci M, et al. Genetics and genomics of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D13–21.

    Article  CAS  PubMed  Google Scholar 

  50. Kerstjens-Frederikse WS, Bongers EM, Roofthooft MT, Leter EM, Douwes JM, Van Dijk A, et al. TBX4 mutations (small patella syndrome) are associated with childhood-onset pulmonary arterial hypertension. J Med Genet. 2013;50(8):500–6.

    Article  CAS  PubMed  Google Scholar 

  51. Nimmakayalu M, Major H, Sheffield V, Solomon DH, Smith RJ, Patil SR, et al. Microdeletion of 17q22q23.2 encompassing TBX2 and TBX4 in a patient with congenital microcephaly, thyroid duct cyst, sensorineural hearing loss, and pulmonary hypertension. Am J Med Genet A. 2011;155a(2):418–23.

    Article  PubMed  Google Scholar 

  52. McDonald J, Wooderchak-Donahue W, VanSant Webb C, Whitehead K, Stevenson DA, Bayrak-Toydemir P. Hereditary hemorrhagic telangiectasia: genetics and molecular diagnostics in a new era. Front Genet. 2015;6:1.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Eyries M, Montani D, Girerd B, Perret C, Leroy A, Lonjou C, et al. EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension. Nat Genet. 2014;46(1):65.

    Article  CAS  PubMed  Google Scholar 

  54. Montani D, Lau EM, Dorfmuller P, Girerd B, Jais X, Savale L, et al. Pulmonary veno-occlusive disease. Eur Respir J. 2016;47(5):1518–34.

    Article  PubMed  Google Scholar 

  55. Gupta N, Vassallo R, Wikenheiser-Brokamp KA, McCormack FX. Diffuse cystic lung disease. Part I. Am J Respir Crit Care Med. 2015;191(12):1354–66.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Gupta N, Vassallo R, Wikenheiser-Brokamp KA, McCormack FX. Diffuse cystic lung disease. Part II. Am J Respir Crit Care Med. 2015;192(1):17–29.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Moss J, Avila NA, Barnes PM, Litzenberger RA, Bechtle J, Brooks PG, et al. Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex. Am J Respir Crit Care Med. 2001;164(4):669–71.

    Article  CAS  PubMed  Google Scholar 

  58. Gupta N, Henske EP. Pulmonary manifestations in tuberous sclerosis complex. Am J Med Genet C Semin Med Genet. 2018;178(3):326–37.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brandner B, Calicchio ML, et al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. 2010;116(11):1919–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Schwentner R, Kolenova A, Jug G, Schnoller T, Ahlmann M, Meister B, et al. Longitudinal assessment of peripheral blood BRAFV600E levels in patients with Langerhans cell histiocytosis. Pediatr Res. 2019;85(6):856–64.

    Article  PubMed  Google Scholar 

  61. Haroche J, Cohen-Aubart F, Emile JF, Arnaud L, Maksud P, Charlotte F, et al. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood. 2013;121(9):1495–500.

    Article  CAS  PubMed  Google Scholar 

  62. Haroche J, Cohen-Aubart F, Emile JF, Donadieu J, Amoura Z. Vemurafenib as first line therapy in BRAF-mutated Langerhans cell histiocytosis. J Am Acad Dermatol. 2015;73(1):e29–30.

    Article  PubMed  Google Scholar 

  63. Heritier S, Jehanne M, Leverger G, Emile JF, Alvarez JC, Haroche J, et al. Vemurafenib use in an infant for high-risk Langerhans cell histiocytosis. JAMA Oncol. 2015;1(6):836–8.

    Article  PubMed  Google Scholar 

  64. Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015;373(8):726–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Boone PM, Scott RM, Marciniak SJ, Henske EP, Raby BA. The genetics of pneumothorax. Am J Respir Crit Care Med. 2019;199:1344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Gupta N, et al. Birt-Hogg-Dubé syndrome. Clin Chest Med. 2016;37(3):475–86.

    Article  PubMed  Google Scholar 

  67. Kennedy JC, et al. Mechanisms of pulmonary cyst pathogenesis in Birt-Hogg-Dube syndrome: the stretch HYPOTHESIS. Semin Cell Dev Biol. 2016;52:47–52.

    Article  CAS  PubMed  Google Scholar 

  68. Gupta N, et al. Spontaneous pneumothoraces in patients with Birt-Hogg-Dubé syndrome. Ann Am Thorac Soc. 2017;14(5):706–13.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Gupta N, Sunwoo BY, Kotloff RM. Birt-Hogg-Dube syndrome. Clin Chest Med. 2016;37(3):475–86.

    Article  PubMed  Google Scholar 

  70. Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Drevinek P, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011;365(18):1663–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, et al. Lumacaftor-Ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med. 2015;373(3):220–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Horani A, Ferkol TW. Advances in the genetics of primary ciliary dyskinesia: clinical implications. Chest. 2018;154(3):645–52.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Shapiro AJ, Josephson M, Rosenfeld M, Yilmaz O, Davis SD, Polineni D, et al. Accuracy of nasal nitric oxide measurement as a diagnostic test for primary ciliary dyskinesia. A systematic review and meta-analysis. Ann Am Thorac Soc. 2017;14(7):1184–96.

    PubMed  PubMed Central  Google Scholar 

  74. American Thoracic Society, European Respiratory Society. American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med. 2003;168(7):818–900.

    Article  Google Scholar 

  75. Torres-Duran M, Lopez-Campos JL, Barrecheguren M, Miravitlles M, Martinez-Delgado B, Castillo S, et al. Alpha-1 antitrypsin deficiency: outstanding questions and future directions. Orphanet J Rare Dis. 2018;13(1):114.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Marciniak SJ, Ordonez A, Dickens JA, Chambers JE, Patel V, Dominicus CS, et al. New concepts in Alpha-1 antitrypsin deficiency disease mechanisms. Ann Am Thorac Soc. 2016;13(Suppl 4):S289–96.

    Article  PubMed  Google Scholar 

  77. Edgar RG, Patel M, Bayliss S, Crossley D, Sapey E, Turner AM. Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review. Int J Chron Obstruct Pulmon Dis. 2017;12:1295–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Lederer DJ, Martinez FJ. Idiopathic pulmonary fibrosis. N Engl J Med. 2018;378(19):1811–23.

    Article  CAS  PubMed  Google Scholar 

  79. Kropski JA, Blackwell TS, Loyd JE. The genetic basis of idiopathic pulmonary fibrosis. Eur Respir J. 2015;45:1717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Allen RJ, Porte J, Braybrooke R, Flores C, Fingerlin TE, Oldham JM, et al. Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study. Lancet Respir Med. 2017;5(11):869–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Fingerlin TE, Murphy E, Zhang W, Peljto AL, Brown KK, Steele MP, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet. 2013;45(6):613–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Noth I, Zhang Y, Ma SF, Flores C, Barber M, Huang Y, et al. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. Lancet Respir Med. 2013;1(4):309–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011;364(16):1503–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Juge PA, Lee JS, Ebstein E, Furukawa H, Dobrinskikh E, Gazal S, et al. MUC5B promoter variant and rheumatoid arthritis with interstitial lung disease. N Engl J Med. 2018;379:2209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Ley B, Newton CA, Arnould I, Elicker BM, Henry TS, Vittinghoff E, et al. The MUC5B promoter polymorphism and telomere length in patients with chronic hypersensitivity pneumonitis: an observational cohort-control study. Lancet Respir Med. 2017;5(8):639–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Peljto AL, Zhang Y, Fingerlin TE, Ma SF, Garcia JG, Richards TJ, et al. Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis. JAMA. 2013;309(21):2232–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Loyd JE. Pulmonary fibrosis in families. Am J Respir Cell Mol Biol. 2003;29(3 Suppl):S47–50.

    CAS  PubMed  Google Scholar 

  88. Steele MP, Speer MC, Loyd JE, Brown KK, Herron A, Slifer SH, et al. Clinical and pathologic features of familial interstitial pneumonia. Am J Respir Crit Care Med. 2005;172(9):1146–52.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Armanios MY, Chen JJ, Cogan JD, Alder JK, Ingersoll RG, Markin C, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007;356(13):1317–26.

    Article  CAS  PubMed  Google Scholar 

  90. Tsakiri KD, Cronkhite JT, Kuan PJ, Xing C, Raghu G, Weissler JC, et al. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci U S A. 2007;104(18):7552–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Cogan JD, Kropski JA, Zhao M, Mitchell DB, Rives L, Markin C, et al. Rare variants in RTEL1 are associated with familial interstitial pneumonia. Am J Respir Crit Care Med. 2015;191:646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Kannengiesser C, Borie R, Menard C, Reocreux M, Nitschke P, Gazal S, et al. Heterozygous RTEL1 mutations are associated with familial pulmonary fibrosis. Eur Respir J. 2015;46(2):474–85.

    Article  CAS  PubMed  Google Scholar 

  93. Stuart BD, Choi J, Zaidi S, Xing C, Holohan B, Chen R, et al. Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening. Nat Genet. 2015;47(5):512–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Kropski JA, Reiss S, Markin C, Brown KK, Schwartz DA, Schwarz MI, et al. Rare genetic variants in PARN are associated with pulmonary fibrosis in families. Am J Respir Crit Care Med. 2017;196(11):1481–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Alder JK, Stanley SE, Wagner CL, Hamilton M, Hanumanthu VS, Armanios M. Exome sequencing identifies mutant TINF2 in a family with pulmonary fibrosis. Chest. 2015;147(5):1361–8.

    Article  PubMed  Google Scholar 

  96. Stanley SE, Gable DL, Wagner CL, Carlile TM, Hanumanthu VS, Podlevsky JD, et al. Loss-of-function mutations in the RNA biogenesis factor NAF1 predispose to pulmonary fibrosis-emphysema. Sci Transl Med. 2016;8(351):351ra107.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Alder JK, Parry EM, Yegnasubramanian S, Wagner CL, Lieblich LM, Auerbach R, et al. Penetrant telomere phenotypes in females with heterozygous mutations in the dyskeratosis congenita 1 (DKC1) gene. Hum Mutat. 2013;34:1481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Kropski JA, Mitchell DB, Markin C, Polosukhin VV, Choi L, Johnson JE, et al. A novel dyskerin (DKC1) mutation is associated with familial interstitial pneumonia. Chest. 2014;146(1):e1–7.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Newton CA, Batra K, Torrealba J, Kozlitina J, Glazer CS, Aravena C, et al. Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive. Eur Respir J. 2016;48(6):1710–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Newton CA, Kozlitina J, Lines JR, Kaza V, Torres F, Garcia CK. Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post-lung transplantation survival. J Heart Lung Transplant. 2017;36(8):845–53.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Faust HE, Golden JA, Rajalingam R, Wang AS, Green G, Hays SR, et al. Short lung transplant donor telomere length is associated with decreased CLAD-free survival. Thorax. 2017;72:1052–4. England: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

    Article  PubMed  Google Scholar 

  102. George G, Rosas IO, Cui Y, McKane C, Hunninghake GM, Camp PC, et al. Short telomeres, telomeropathy, and subclinical extrapulmonary organ damage in patients with interstitial lung disease. Chest. 2015;147(6):1549–57.

    Article  PubMed  Google Scholar 

  103. Silhan LL, Shah PD, Chambers DC, Snyder LD, Riise GC, Wagner CL, et al. Lung transplantation in telomerase mutation carriers with pulmonary fibrosis. Eur Respir J. 2014;44(1):178–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Tokman S, Singer JP, Devine MS, Westall GP, Aubert JD, Tamm M, et al. Clinical outcomes of lung transplant recipients with telomerase mutations. J Heart Lung Transplant. 2015;34(10):1318–24.

    Article  PubMed  PubMed Central  Google Scholar 

  105. El-Chemaly S, Young LR. Hermansky-Pudlak syndrome. Clin Chest Med. 2016;37(3):505–11.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Jonathan A. Kropski

  2. Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA

    Jonathan A. Kropski

  3. Department of Veterans Affairs Medical Center, Nashville, TN, USA

    Jonathan A. Kropski

Authors
  1. Jonathan A. Kropski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan A. Kropski .

Editor information

Editors and Affiliations

  1. Assistant Professor Pulmonary, Critical Care and Sleep Medicine Section, Department of Medicine, Yale University School of Medicine, New Haven, CT, USA

    Jose L. Gomez

  2. Assistant Professor of Informatics, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA

    Blanca E. Himes

  3. Boehringer-Ingelheim Endowed, Professor of Internal Medicine, Chief of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA

    Naftali Kaminski

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kropski, J.A. (2020). Differential Diagnosis of Diffuse Pulmonary Disorders Using Genetics. In: Gomez, J., Himes, B., Kaminski, N. (eds) Precision in Pulmonary, Critical Care, and Sleep Medicine. Respiratory Medicine. Humana, Cham. https://doi.org/10.1007/978-3-030-31507-8_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-31507-8_2

  • Published:

  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-030-31506-1

  • Online ISBN: 978-3-030-31507-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation