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Semin Respir Crit Care Med 2002; 23(2): 177-188
DOI: 10.1055/s-2002-25306
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Genetics of Pulmonary Fibrosis

Mark M. Wurfel, Ganesh Raghu
  • Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, Washington
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Publikationsdatum:
24. April 2002 (online)

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ABSTRACT

Pulmonary fibrosis is a devastating disease that occurs in association with environmental exposures, several inherited diseases, collagen vascular disease, as well as in an idiopathic form. Epithelial cell damage, excessive fibroblast proliferation, upregulation of extracellular matrix production, and attenuated matrix degradation are shared pathophysiological features of these different forms of pulmonary fibrosis. Several observations suggest that genetic predisposition plays an important role in the pathophysiology of pulmonary fibrosis. There is significant inter-individual variation in the degree of pulmonary fibrosis resulting from exposure to similar levels of an inhaled fibrogenic agent. There are several inherited diseases with known genetic mutations that have high rates of pulmonary fibrosis. Idiopathic pulmonary fibrosis can occur in multiple first-degree relatives, including those separated at an early age. Finally, recent studies have identified polymorphisms within genes for cytokines, histocompatability antigens, and extracellular matrix components that are associated with the development of pulmonary fibrosis. Identification of putative pulmonary fibrosis gene/s (PF gene/s) may result in novel diagnostic and therapeutic interventions for those at risk for development of pulmonary fibrosis.

KEYWORD

Pulmonary fibrosis - usual interstitial pneumonitis - genetic predisposition - inherited disorders - fibroproliferation

REFERENCES

  • 1 Selman M, King T E, Pardo A. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy.  Ann Intern Med . 2001;  134 136-151
    CrossrefPubMedGoogle Scholar
  • 2 Wagner G R. Asbestosis and silicosis.  Lancet . 1997;  349 1311-1315
    CrossrefPubMedGoogle Scholar
  • 3 NIOSH. NIOSH Alert: Request for Assistance in Preventing Silicosis and Deaths from Sandblasting.  Cincinnati, Ohio: DHHS National Institute for Occupational Safety and Health 1996: 92-102
    Google Scholar
  • 4 Landrigan P. Silicosis.  Occup Med State Art Rev . 1987;  2 319-326
    PubMedGoogle Scholar
  • 5 Mossman B T, Churg A. Mechanisms in the pathogenesis of asbestosis and silicosis.  Am J Respir Crit Care Med . 1998;  157 1666-1680
    PubMedGoogle Scholar
  • 6 Nagelschmidt G. The relation between lung dust and lung pathology in pneumoconiosis.  Br J Ind Med . 1960;  17 247-259
    PubMedGoogle Scholar
  • 7 Piguet P F, Collart M A, Grau G E. Requirement of tumour necrosis factor for development of silica-induced pulmonary fibrosis.  Nature . 1990;  344 245-247
    CrossrefPubMedGoogle Scholar
  • 8 Davis G S, Pfeiffer L M, Hemenway D R. Persistent overexpression of interleukin-1beta and tumor necrosis factor-alpha in murine silicosis.  J Environ Pathol Toxicol Oncol . 1998;  17 99-114
    PubMedGoogle Scholar
  • 9 Piguet P F, Vesin C, Grau G E. Interleukin 1 receptor antagonist (IL-1ra) prevents or cures pulmonary fibrosis elicited in mice by bleomycin or silica.  Cytokine . 1993;  5 57-61
    CrossrefPubMedGoogle Scholar
  • 10 Mariani T J, Roby J D, Mecham R P. Localization of type I procollagen gene expression in silica-induced granulomatous lung disease and implication of transforming growth factor-beta as a mediator of fibrosis.  Am J Pathol . 1996;  148 151-164
    PubMedGoogle Scholar
  • 11 Yucesoy B, Vallyathan V, Landsittel D P. Polymorphisms of the IL-1 gene complex in coal miners with silicosis.  Am J Ind Med . 2001;  39 286-291
    CrossrefPubMedGoogle Scholar
  • 12 Yucesoy B, Vallyathan V, Landsittel D P. Association of tumor necrosis factor-alpha and interleukin-1 gene polymorphisms with silicosis.  Toxicol Appl Pharmacol . 2001;  172 75-82
    CrossrefPubMedGoogle Scholar
  • 13 Kreiss K, Danilovs J A, Newman L S. Histocompatibility antigens in a population based silicosis series.  Br J Ind Med . 1989;  46 364-369
    PubMedGoogle Scholar
  • 14 Honda K, Kimura A, Dong R P. Immunogenetic analysis of silicosis in Japan.  Am J Respir Cell Mol Biol . 1993;  8 106-111
    PubMedGoogle Scholar
  • 15 Brodkin C A, Barnhart S, Anderson G. Correlation between respiratory symptoms and pulmonary function in asbestos-exposed workers.  Am Rev Respir Dis . 1993;  148 32-37
    PubMedGoogle Scholar
  • 16 ATS. American Thoracic Society. Medical Section of the American Lung Association: the diagnosis of nonmalignant diseases related to asbestos.  Am Rev Respir Dis . 1986;  134 363-368
    PubMedGoogle Scholar
  • 17 Staples C A. Computed tomography in the evaluation of benign asbestos-related disorders.  Radiol Clin North Am . 1992;  30 1191-1207
    PubMedGoogle Scholar
  • 18 Craighead J E, Abraham J L, Churg A. The pathology of asbestos-associated diseases of the lungs and pleural cavities: diagnostic criteria and proposed grading schema. Report of the Pneumoconiosis Committee of the College of American Pathologists and the National Institute for Occupational Safety and Health.  Arch Pathol Lab Med . 1982;  106 544-596
    PubMedGoogle Scholar
  • 19 Browne K. Asbestos-related disorders. In: Parkes WR, ed. Occupational Lung Disorders 3rd ed. Oxford: Butterworth-Heinemann 1994: 411-504
    Google Scholar
  • 20 Merchant J A, Klouda P T, Soutar C A. The HL-A system in asbestos workers.  Br Med J . 1975;  1 189-191
    PubMedGoogle Scholar
  • 21 Matej H, Lange A, Smolik R. HLA antigens in asbestosis.  Arch Immunol Ther Exp (Warsz) . 1977;  25 489-491
    PubMedGoogle Scholar
  • 22 Gregor A, Singh S, Turner-Warwick M. The role of histocompatibility (HLA) antigens in asbestosis.  Br J Dis Chest . 1979;  73 245-252
    PubMedGoogle Scholar
  • 23 Turner-Warwick M. HLA phenotypes in asbestos workers.  Br J Dis Chest . 1979;  73 243-244
    PubMedGoogle Scholar
  • 24 Begin R, Menard H, Decarie F. Immunogenetic factors as determinants of asbestosis.  Lung . 1987;  165 159-163
    PubMedGoogle Scholar
  • 25 Darke C, Wagner M M, McMillan G H. HLA-A and B antigen frequencies in an asbestos exposed population with normal and abnormal chest radiographs.  Tissue Antigens . 1979;  13 228-232
    PubMedGoogle Scholar
  • 26 Evans C C, Lewinsohn H C, Evans J M. Frequency of HLA antigen in asbestos workers with and without pulmonary fibrosis.  Br Med J . 1977;  1 603-605
    PubMedGoogle Scholar
  • 27 Shih J F, Hunninghake G W, Goeken N E. The relationship between HLA-A, B, DQ, and DR antigens and asbestos-induced lung disease.  Chest . 1993;  104 26-31
    PubMedGoogle Scholar
  • 28 Zhang Y, Lee T C, Guillemin B. Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure.  J Immunol . 1993;  150 4188-4196
    PubMedGoogle Scholar
  • 29 Bissonnette E, Rola-Pleszczynski M. Pulmonary inflammation and fibrosis in a murine model of asbestosis and silicosis: possible role of tumor necrosis factor.  Inflammation . 1989;  13 329-339
    CrossrefPubMedGoogle Scholar
  • 30 Briggs D C, Vaughan R W, Welsh K I. Immunogenetic prediction of pulmonary fibrosis in systemic sclerosis.  Lancet . 1991;  338 661-662
    CrossrefPubMedGoogle Scholar
  • 31 King T E. Connective tissue disease. In: Schwarz MI, King TE, eds. Interstitial lung disease St. Louis: Mosby-Year Book 1993: 271-308
    Google Scholar
  • 32 Valentini G. Classification of systemic sclerosis.  Clin Dermatol . 1994;  12 217-223
    PubMedGoogle Scholar
  • 33 Mitchell H, Bolster M B, LeRoy E C. Scleroderma and related conditions.  Med Clin North Am . 1997;  81 129-149
    CrossrefPubMedGoogle Scholar
  • 34 D'Angelo W A, Fries J F, Masi A T. Pathologic observations in systemic sclerosis (scleroderma): a study of fifty-eight autopsy cases and fifty-eight matched controls.  Am J Med . 1969;  46 428-440
    CrossrefPubMedGoogle Scholar
  • 35 Warrick J H, Bhalla M, Schabel S I. High resolution computed tomography in early scleroderma lung disease.  J Rheumatol . 1991;  18 1520-1528
    PubMedGoogle Scholar
  • 36 Silver R M, Warrick J H, Kinsella M B. Cyclophosphamide and low-dose prednisone therapy in patients with systemic sclerosis (scleroderma) with interstitial lung disease.  J Rheumatol . 1993;  20 838-844
    PubMedGoogle Scholar
  • 37 Akesson A, Scheja A, Lundin A. Improved pulmonary function in systemic sclerosis after treatment with cyclophosphamide.  Arthritis Rheum . 1994;  37 729-735
    CrossrefPubMedGoogle Scholar
  • 38 Lynch C J, Singh G, Whiteside T L. Histocompatibility antigens in progressive systemic sclerosis (PSS; scleroderma).  J Clin Immunol . 1982;  2 314-318
    CrossrefPubMedGoogle Scholar
  • 39 Bianchi D W, Zickwolf G K, Weil G J. Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum.  Proc Natl Acad Sci U S A . 1996;  93 705-708
    CrossrefPubMedGoogle Scholar
  • 40 Nelson J L, Furst D E, Maloney S. Microchimerism and HLA-compatible relationships of pregnancy in scleroderma.  Lancet . 1998;  351 559-562
    CrossrefPubMedGoogle Scholar
  • 41 Maloney S, Smith A, Furst D E. Microchimerism of maternal origin persists into adult life.  J Clin Invest . 1999;  104 41-47
    PubMedGoogle Scholar
  • 42 Avila J J, Lympany P A, Pantelidis P. Fibronectin gene polymorphisms associated with fibrosing alveolitis in systemic sclerosis.  Am J Respir Cell Mol Biol . 1999;  20 106-112
    PubMedGoogle Scholar
  • 43 Limper A H, Roman J. Fibronectin: a versatile matrix protein with roles in thoracic development, repair and infection.  Chest . 1992;  101 1663-1673
    CrossrefPubMedGoogle Scholar
  • 44 Bitterman P, Rennard S, Adelberg S. Role of fibronectin in fibrotic lung disease: a growth factor for human lung fibroblasts.  Chest . 1983;  83 96S
    PubMedGoogle Scholar
  • 45 ATS. American Thoracic Society.  Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med . 2000;  161 646-664
    PubMedGoogle Scholar
  • 46 Ortiz L A, Lasky J, Lungarella G. Upregulation of the p75 but not the p55 TNF-alpha receptor mRNA after silica and bleomycin exposure and protection from lung injury in double receptor knockout mice.  Am J Respir Cell Mol Biol . 1999;  20 825-833
    PubMedGoogle Scholar
  • 47 Munger J S, Huang X, Kawakatsu H. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis.  Cell . 1999;  96 319-328
    CrossrefPubMedGoogle Scholar
  • 48 Ziegenhagen M W, Schrum S, Zissel G. Increased expression of proinflammatory chemokines in bronchoalveolar lavage cells of patients with progressing idiopathic pulmonary fibrosis and sarcoidosis.  J Investig Med . 1998;  46 223-231
    PubMedGoogle Scholar
  • 49 Coker R K, Laurent G J, Jeffery P K. Localisation of transforming growth factor beta1 and beta3 mRNA transcripts in normal and fibrotic human lung.  Thorax . 2001;  56 549-556
    CrossrefPubMedGoogle Scholar
  • 50 Peabody J W. Idiopathic pulmonary fibrosis: its occurance in identical twin sisters.  Dis Chest . 1950;  18 330-334
    PubMedGoogle Scholar
  • 51 Javaheri S, Lederer D H, Pella J A. Idiopathic pulmonary fibrosis in monozygotic twins: the importance of genetic predisposition.  Chest . 1980;  78 591-594
    PubMedGoogle Scholar
  • 52 Swaye P, Van Ordstrand S H, McCormack L J. Familial Hamman-Rich syndrome: report of eight cases.  Dis Chest . 1969;  55 7-12
    PubMedGoogle Scholar
  • 53 Turton C W, Morris L M, Lawler S D. HLA in cryptogenic fibrosing alveolitis.  Lancet . 1978;  1 507-508
    PubMedGoogle Scholar
  • 54 Evans C C. HLA antigens in diffuse fibrosing alveolitis.  Thorax . 1976;  31 483
    PubMedGoogle Scholar
  • 55 Libby D M, Gibofsky A, Fotino M. Immunogenetic and clinical findings in idiopathic pulmonary fibrosis: association with the B-cell alloantigen HLA-DR2.  Am Rev Respir Dis . 1983;  127 618-622
    PubMedGoogle Scholar
  • 56 Musk A W, Zilko P J, Manners P. Genetic studies in familial fibrosing alveolitis: possible linkage with immunoglobulin allotypes (Gm).  Chest . 1986;  89 206-210
    CrossrefPubMedGoogle Scholar
  • 57 Whyte M, Hubbard R, Meliconi R. Increased risk of fibrosing alveolitis associated with interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphisms.  Am J Respir Crit Care Med . 2000;  162 755-758
    CrossrefPubMedGoogle Scholar
  • 58 Wilson A G, Symons J A, McDowell T L. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation.  Proc Natl Acad Sci U S A . 1997;  94 3195-3199
    CrossrefPubMedGoogle Scholar
  • 59 Danis V A, Millington M, Hyland V J. Cytokine production by normal human monocytes: inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism.  Clin Exp Immunol . 1995;  99 303-310
    PubMedGoogle Scholar
  • 60 Pantelidis P, Fanning G C, Wells A U. Analysis of tumor necrosis factor-alpha, lymphotoxin-alpha, tumor necrosis factor receptor II, and interleukin-6 polymorphisms in patients with idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med . 2001;  163 1432-1436
    CrossrefPubMedGoogle Scholar
  • 61 Raghu G, Hert R. Interstitial lung disease: genetic predisposition and inherited interstitial lung disease.  Sem Respir Critical Care Med . 1993;  14 323-332
    PubMedGoogle Scholar
  • 62 Sandoz E. Uber zwei Falle von fotaler Bronchektasie.  Beitr Pathol Anat . 1907;  41 496-517
    PubMedGoogle Scholar
  • 63 Marshall R P, Puddicombe A, Cookson W O. Adult familial cryptogenic fibrosing alveolitis in the United Kingdom.  Thorax . 2000;  55 143-146
    CrossrefPubMedGoogle Scholar
  • 64 Barzo P. Familial idiopathic fibrosing alveolitis.  Eur J Respir Dis . 1985;  66 350-352
    PubMedGoogle Scholar
  • 65 Hwang H C, Raghu G, Schmidt R. Pathologic features of familial versus sporadic cases of idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med . 1997;  155 A323
    PubMedGoogle Scholar
  • 66 Raghu G. Genetic study of idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med . 1996;  153 A689
    PubMedGoogle Scholar
  • 67 Uchiyama E A. Unexpectedly high incidence of idiopathic pulmonary fibrosis among siblings of patients with IPF in Japan (Abstract).  Am J Respir Crit Care Med . 1995;  153 A405
    PubMedGoogle Scholar
  • 68 Johnston I D, Prescott R J, Chalmers J C. British Thoracic Society study of cryptogenic fibrosing alveolitis: current presentation and initial management. Fibrosing Alveolitis Subcommittee of the Research Committee of the British Thoracic Society.  Thorax . 1997;  52 38-44
    CrossrefPubMedGoogle Scholar
  • 69 Bitterman P B, Rennard S I, Keogh B A. Familial idiopathic pulmonary fibrosis: evidence of lung inflammation in unaffected family members.  N Engl J Med . 1986;  314 1343-1347
    CrossrefPubMedGoogle Scholar
  • 70 Hermansky F, Pudlak P. Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: report of two cases with histochemical studies.  Blood . 1959;  14 162-169
    PubMedGoogle Scholar
  • 71 Gahl W A, Brantly M, Kaiser-Kupfer M I. Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome).  N Engl J Med . 1998;  338 1258-1264
    CrossrefPubMedGoogle Scholar
  • 72 Harmon K R, Witkop C J, White J G. Pathogenesis of pulmonary fibrosis: platelet-derived growth factor precedes structural alterations in the Hermansky-Pudlak syndrome.  J Lab Clin Med . 1994;  123 617-627
    PubMedGoogle Scholar
  • 73 Garay S M, Gardella J E, Fazzini E P. Hermansky-Pudlak syndrome: pulmonary manifestations of a ceroid storage disorder.  Am J Med . 1979;  66 737-747
    CrossrefPubMedGoogle Scholar
  • 74 Schinella R A, Greco M A, Cobert B L. Hermansky-Pudlak syndrome with granulomatous colitis.  Ann Intern Med . 1980;  92 20-23
    PubMedGoogle Scholar
  • 75 Witkop C J, Nunez Babcock M, Rao G H. Albinism and Hermansky-Pudlak syndrome in Puerto Rico.  Bol Asoc Med P R . 1990;  82 333-339
    PubMedGoogle Scholar
  • 76 Witkop C J, Quevedo W C, Fitzpatrick T B. Albinism. In: Scriver CR, Beaudet AL, Sly WS, et al, eds. The metabolic basis of inherited disease New York: McGraw-Hill 1989
    Google Scholar
  • 77 Oh J, Bailin T, Fukai K. Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles.  Nat Genet . 1996;  14 300-306
    PubMedGoogle Scholar
  • 78 Oetting W S, King R A. Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism.  Hum Mutat . 1999;  13 99-115
    CrossrefPubMedGoogle Scholar
  • 79 Brantly M, Avila N A, Shotelersuk V. Pulmonary function and high-resolution CT findings in patients with an inherited form of pulmonary fibrosis, Hermansky-Pudlak syndrome, due to mutations in HPS-1.  Chest . 2000;  117 129-136
    CrossrefPubMedGoogle Scholar
  • 80 Davies B H, Tuddenham E G. Familial pulmonary fibrosis associated with oculocutaneous albinism and platelet function defect: a new syndrome.  Q J Med . 1976;  45 219-232
    PubMedGoogle Scholar
  • 81 Leitman B S, Balthazar E J, Garay S M. The Hermansky-Pudlak syndrome: radiographic features.  Can Assoc Radiol J . 1986;  37 42-45
    PubMedGoogle Scholar
  • 82 Hoyle G W, Li J, Finkelstein J B. Emphysematous lesions, inflammation, and fibrosis in the lungs of transgenic mice overexpressing platelet-derived growth factor.  Am J Pathol . 1999;  154 1763-1775
    PubMedGoogle Scholar
  • 83 Minai O A, Sullivan E J, Stoller J K. Pulmonary involvement in Niemann-Pick disease: case report and literature review.  Respir Med . 2000;  94 1241-1251
    PubMedGoogle Scholar
  • 84 Kolodny E H. Niemann-Pick disease.  Curr Opin Hematol . 2000;  7 48-52
    CrossrefPubMedGoogle Scholar
  • 85 Lachman R, Crocker A, Schulman J. Radiological findings in Niemann-Pick disease.  Radiology . 1973;  108 659-664
    PubMedGoogle Scholar
  • 86 Schofer O, Mischo B, Puschel W. Early-lethal pulmonary form of Niemann-Pick type C disease belonging to a second, rare genetic complementation group.  Eur J Pediatr . 1998;  157 45-49
    PubMedGoogle Scholar
  • 87 Skikne M I, Prinsloo I, Webster I. Electron microscopy of lung in Niemann-Pick disease.  J Pathol . 1972;  106 119-122
    PubMedGoogle Scholar
  • 88 Lever A M, Ryder J B. Cor pulmonale in an adult secondary to Niemann-Pick disease.  Thorax . 1983;  38 873-874
    PubMedGoogle Scholar
  • 89 Charrow J, Esplin J A, Gribble T J. Gaucher disease: recommendations on diagnosis, evaluation, and monitoring.  Arch Intern Med . 1998;  158 1754-1760
    CrossrefPubMedGoogle Scholar
  • 90 Charrow J, Andersson H C, Kaplan P. The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease.  Arch Intern Med . 2000;  160 2835-2843
    CrossrefPubMedGoogle Scholar
  • 91 Schneider E L, Epstein C J, Kaback M J. Severe pulmonary involvement in adult Gaucher's disease: report of three cases and review of the literature.  Am J Med . 1977;  63 475-480
    CrossrefPubMedGoogle Scholar
  • 92 Dawson A, Elias D J, Rubenson D. Pulmonary hypertension developing after alglucerase therapy in two patients with type 1 Gaucher disease complicated by the hepatopulmonary syndrome.  Ann Intern Med . 1996;  125 901-904
    PubMedGoogle Scholar
  • 93 Banjar H. Pulmonary involvement of Gaucher's disease in children: a common presentation in Saudi Arabia.  Ann Trop Paediatr . 1998;  18 55-59
    PubMedGoogle Scholar
  • 94 Castro M, Shepherd C W, Gomez M R. Pulmonary tuberous sclerosis.  Chest . 1995;  107 189-195
    CrossrefPubMedGoogle Scholar
  • 95 Chan J K, Tsang W Y, Pau M Y. Lymphangiomyomatosis and angiomyolipoma: closely related entities characterized by hamartomatous proliferation of HMB-45-positive smooth muscle.  Histopathology . 1993;  22 445-455
    PubMedGoogle Scholar
  • 96 Carbonara C, Longa L, Grosso E. Apparent preferential loss of heterozygosity at TSC2 over TSC1 chromosomal region in tuberous sclerosis hamartomas.  Genes Chromosomes Cancer . 1996;  15 18-25
    CrossrefPubMedGoogle Scholar
  • 97 Carbonara C, Longa L, Grosso E. 9q34 loss of heterozygosity in a tuberous sclerosis astrocytoma suggests a growth suppressor-like activity also for the TSC1 gene.  Hum Mol Genet . 1994;  3 1829-1832
    PubMedGoogle Scholar
  • 98 Smolarek T A, Wessner L L, McCormack F X. Evidence that lymphangiomyomatosis is caused by TSC2 mutations: chromosome 16p13 loss of heterozygosity in angiomyolipomas and lymph nodes from women with lymphangiomyomatosis.  Am J Hum Genet . 1998;  62 810-815
    CrossrefPubMedGoogle Scholar
  • 99 Astrinidis A, Khare L, Carsillo T. Mutational analysis of the tuberous sclerosis gene TSC2 in patients with pulmonary lymphangioleiomyomatosis.  J Med Genet . 2000;  37 55-57
    PubMedGoogle Scholar
  • 100 Carsillo T, Astrinidis A, Henske E P. Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis.  Proc Natl Acad Sci U S A . 2000;  97 6085-6090
    CrossrefPubMedGoogle Scholar
  • 101 Mulvihill J J, Parry D M, Sherman J L. NIH conference. Neurofibromatosis 1 (Recklinghausen disease) and neurofibromatosis 2 (bilateral acoustic neurofibromatosis): an update.  Ann Intern Med . 1990;  113 39-52
    CrossrefPubMedGoogle Scholar
  • 102 Li Y, O'Connell P, Breidenbach H H. Genomic organization of the neurofibromatosis 1 gene (NF1).  Genomics . 1995;  25 9-18
    CrossrefPubMedGoogle Scholar
  • 103 Kloos R T, Rufini V, Gross M D. Bone scans in neurofibromatosis: neurofibroma, plexiform neuroma and neurofibrosarcoma.  J Nucl Med . 1996;  37 1778-1783
    PubMedGoogle Scholar
  • 104 Evans D G, Huson S M, Donnai D. A clinical study of type 2 neurofibromatosis.  Q J Med . 1992;  84 603-618
    PubMedGoogle Scholar
  • 105 De Vitis R L, Tedde A, Vitelli F. Analysis of the neurofibromatosis type 2 gene in different human tumors of neuroectodermal origin.  Hum Genet . 1996;  97 638-641
    PubMedGoogle Scholar
  • 106 Colman S D, Rasmussen S A, Ho V T. Somatic mosaicism in a patient with neurofibromatosis type 1.  Am J Hum Genet . 1996;  58 484-490
    PubMedGoogle Scholar
  • 107 Davis S A, Kaplan R L. Neurofibromatosis and interstitial lung disease.  Arch Dermatol . 1978;  114 1368-1369
    CrossrefPubMedGoogle Scholar
  • 108 Webb W R, Goodman P C. Fibrosing alveolitis in patients with neurofibromatosis.  Radiology . 1977;  122 289-293
    PubMedGoogle Scholar
  • 109 Meyer F J, Teschler H, Schnabel R. Bronchoalveolar lavage cytology in pulmonary fibrosis associated with neurofibromatosis.  Respir Med . 1996;  90 365-367
    PubMedGoogle Scholar
  • 110 Massaro D, Katz S. Fibrosing alveolitis: its occurrence, roentgenographic, and pathologic features in von Recklinghausen's neurofibromatosis.  Am Rev Respir Dis . 1966;  93 934-942
    PubMedGoogle Scholar
  • 111 Atit R P, Crowe M J, Greenhalgh D G. The Nf1 tumor suppressor regulates mouse skin wound healing, fibroblast proliferation, and collagen deposited by fibroblasts.  J Invest Dermatol . 1999;  112 835-842
    CrossrefPubMedGoogle Scholar
  • 112 Foley Jr P T, Harrison H C, Arnaud C D. Familial benign hypercalcemia.  J Pediatr . 1972;  81 1060-1067
    PubMedGoogle Scholar
  • 113 Marx S J, Attie M F, Levine M A. The hypocalciuric or benign variant of familial hypercalcemia: clinical and biochemical features in fifteen kindreds.  Medicine (Baltimore) . 1981;  60 397-412
    CrossrefPubMedGoogle Scholar
  • 114 Brown E M. Familial hypocalciuric hypercalcemia and other disorders with resistance to extracellular calcium.  Endocrinol Metab Clin North Am . 2000;  29 503-522
    CrossrefPubMedGoogle Scholar
  • 115 Demedts M, Auwerx J, Goddeeris P. The inherited association of interstitial lung disease, hypocalciuric hypercalcemia, and defective granulocyte function.  Am Rev Respir Dis . 1985;  131 470-475
    PubMedGoogle Scholar
  • 116 Auwerx J, Boogaerts M, Ceuppens J L. Defective host defence mechanisms in a family with hypocalciuric hypercalcaemia and coexisting interstitial lung disease.  Clin Exp Immunol . 1985;  62 57-64
    PubMedGoogle Scholar