title: Genetic Basis of Children's Interstitial Lung Disease.
abstract: Specific genetic causes for children's interstitial lung disease (chILD) have been identified within the past decade. These include deletions of or mutations in genes encoding proteins important in surfactant production and function (SP-B, SP-C, and ABCA3), surfactant catabolism (GM-CSF receptor), as well as transcription factors important for surfactant production (TTF1) or lung development (Fox F1), with heterozygous deletions or loss-of-function mutations of the latter resulting in alveolar capillary dysplasia (ACD) with misalignment of the pulmonary veins. Familial pulmonary fibrosis in adults may result from mutations in genes encoding components of telomerase and SP-A2. While not yet reported in children, the expression of these genes in alveolar type II epithelial cells supports a key role for the disruption of normal homeostasis in this cell type in the pathogenesis of interstitial lung disease. The identification of specific genetic causes for chILD now allows for the possibility of non-invasive diagnosis, and provides insight into basic cellular mechanisms that may allow the development of novel therapies.
authors.affiliation: Department of Pediatrics, Division of Neonatology,  Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Nogee
references.citation: Hum Mol Genet. 2002 Apr 15;11(8):971-9
references.pmid: 11971878
references.citation: Crit Care Med. 1993 Apr;21(4):628-30
references.pmid: 8472585
references.citation: Immunity. 1995 Mar;2(3):211-22
references.pmid: 7697542
references.citation: Am J Respir Cell Mol Biol. 2004 Jun;30(6):771-6
references.pmid: 14656744
references.citation: Biochim Biophys Acta. 1998 Nov 19;1408(2-3):79-89
references.pmid: 9813251
references.citation: Pediatr Pathol. 1991 Jan-Feb;11(1):163-70
references.pmid: 2014189
references.citation: Chest. 2002 Mar;121(3 Suppl):20S-21S
references.pmid: 11893657
references.citation: Pediatr Res. 2006 Jun;59(6):801-5
references.pmid: 16641205
references.citation: Genome Res. 2001 Jul;11(7):1156-66
references.pmid: 11435397
references.citation: Pediatr Res. 2008 Jun;63(6):645-9
references.pmid: 18317237
references.citation: Am J Respir Crit Care Med. 2005 Oct 15;172(8):1026-31
references.pmid: 15976379
references.citation: Biochim Biophys Acta. 1998 Nov 19;1408(2-3):173-9
references.pmid: 9813310
references.citation: J Lipid Res. 2007 Mar;48(3):621-32
references.pmid: 17142808
references.citation: Am J Respir Cell Mol Biol. 2005 Jun;32(6):521-30
references.pmid: 15778495
references.citation: Thyroid. 2008 Sep;18(9):1005-9
references.pmid: 18788921
references.citation: FEBS Lett. 2007 Jul 10;581(17):3139-44
references.pmid: 17574245
references.citation: Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):973-81
references.pmid: 10712351
references.citation: Am J Physiol Lung Cell Mol Physiol. 2008 Oct;295(4):L698-707
references.pmid: 18676873
references.citation: J Pediatr. 2000 Aug;137(2):272-6
references.pmid: 10931427
references.citation: J Pediatr. 2004 Nov;145(5):646-51
references.pmid: 15520767
references.citation: J Clin Endocrinol Metab. 2006 May;91(5):1832-41
references.pmid: 16507635
references.citation: J Pediatr. 2007 Sep;151(3):322-4
references.pmid: 17719949
references.citation: Pediatr Res. 2000 Sep;48(3):275-82
references.pmid: 10960490
references.citation: J Biol Chem. 2003 Dec 26;278(52):52739-46
references.pmid: 14525980
references.citation: Pediatr Res. 2007 Aug;62(2):176-9
references.pmid: 17597647
references.citation: N Engl J Med. 1998 Apr 30;338(18):1317-8
references.pmid: 9565498
references.citation: Semin Cell Dev Biol. 2002 Aug;13(4):263-70
references.pmid: 12243725
references.citation: J Pediatr. 1997 Feb;130(2):231-9
references.pmid: 9042125
references.citation: N Engl J Med. 2005 Jan 13;352(2):207-8
references.pmid: 15647591
references.citation: J Exp Med. 2008 Nov 24;205(12):2703-10
references.pmid: 18955570
references.citation: Pediatr Pulmonol. 1993 Sep;16(3):184-96
references.pmid: 8309744
references.citation: Am Rev Respir Dis. 1975 May;111(5):657-88
references.pmid: 1093459
references.citation: FEBS Lett. 2001 Nov 16;508(2):221-5
references.pmid: 11718719
references.citation: Acta Paediatr. 2007 Feb;96(2):185-90
references.pmid: 17429902
references.citation: J Pediatr. 2007 Jun;150(6):649-53, 653.e1
references.pmid: 17517255
references.citation: Thorax. 2008 Apr;63(4):366-73
references.pmid: 18024538
references.citation: Pediatr Pulmonol. 2002 Jul;34(1):23-9
references.pmid: 12112793
references.citation: Ultrastruct Pathol. 2005 Nov-Dec;29(6):503-9
references.pmid: 16316951
references.citation: Chest. 1993 Oct;104(4):1176-82
references.pmid: 8404187
references.citation: Nat Genet. 1999 Mar;21(3):297-301
references.pmid: 10080183
references.citation: Proc Natl Acad Sci U S A. 2007 May 1;104(18):7552-7
references.pmid: 17460043
references.citation: Mod Pathol. 2007 Oct;20(10):1009-18
references.pmid: 17660803
references.citation: Am J Respir Crit Care Med. 2007 Dec 1;176(11):1120-8
references.pmid: 17885266
references.citation: Pediatr Pulmonol. 2009 Feb;44(2):167-75
references.pmid: 19148933
references.citation: Hum Mol Genet. 2009 Jun 15;18(12):2266-76
references.pmid: 19336474
references.citation: Eur J Pediatr. 2008 Jun;167(6):691-3
references.pmid: 17618459
references.citation: Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9565-9
references.pmid: 7568173
references.citation: Immunity. 2001 Oct;15(4):557-67
references.pmid: 11672538
references.citation: J Pediatr. 2006 Oct;149(4):548-53
references.pmid: 17011330
references.citation: Am J Hum Genet. 2009 Jun;84(6):780-91
references.pmid: 19500772
references.citation: Am J Med Genet A. 2006 Jan 1;140(1):62-9
references.pmid: 16333843
references.citation: Annu Rev Physiol. 2005;67:663-96
references.pmid: 15709974
references.citation: Am J Med Genet A. 2003 Jun 15;119A(3):324-39
references.pmid: 12784301
references.citation: J Pediatr. 2005 Mar;146(3):370-5
references.pmid: 15756222
references.citation: Biochim Biophys Acta. 2006 May;1762(5):510-24
references.pmid: 16540294
references.citation: Am J Respir Crit Care Med. 2008 Oct 1;178(7):729-37
references.pmid: 18635888
references.citation: Histopathology. 1995 Aug;27(2):192-4
references.pmid: 8835270
references.citation: Am J Respir Crit Care Med. 2006 Sep 1;174(5):571-80
references.pmid: 16728712
references.citation: Blood. 2004 Feb 1;103(3):1089-98
references.pmid: 14512323
references.citation: Am J Hum Genet. 2009 Jan;84(1):52-9
references.pmid: 19100526
references.citation: Annu Rev Physiol. 2001;63:555-78
references.pmid: 11181967
references.citation: Biochem Biophys Res Commun. 2004 Oct 15;323(2):547-55
references.pmid: 15369786
references.citation: J Pediatr. 1993 Aug;123(2):275-8
references.pmid: 8345427
references.citation: J Perinatol. 2006 Jan 1;26(1):67-70
references.pmid: 16355106
references.citation: J Pediatr. 1999 May;134(5):661-2
references.pmid: 10228309
references.citation: Biochem J. 2008 Dec 1;416(2):201-9
references.pmid: 18643778
references.citation: J Med Genet. 2009 Jul;46(7):490-4
references.pmid: 19443464
references.citation: J Pediatr. 2009 Dec;155(6):854-859.e1
references.pmid: 19647838
references.citation: Mov Disord. 2006 Dec;21(12):2237-40
references.pmid: 17044090
references.citation: Pediatr Res. 1986 May;20(5):460-7
references.pmid: 3754957
references.citation: J Clin Invest. 2002 Feb;109(4):469-73
references.pmid: 11854318
references.citation: J Clin Invest. 1997 Nov 1;100(9):2211-7
references.pmid: 9410898
references.citation: Annu Rev Physiol. 2001;63:495-519
references.pmid: 11181965
references.citation: Annu Rev Med. 2010;61:105-19
references.pmid: 19824815
references.citation: J Exp Med. 2008 Nov 24;205(12):2711-6
references.pmid: 18955567
references.citation: Annu Rev Physiol. 2001;63:521-54
references.pmid: 11181966
references.citation: J Biol Chem. 2006 Nov 10;281(45):34503-14
references.pmid: 16959783
references.citation: J Pediatr. 2004 Aug;145(2):268-72
references.pmid: 15289783
references.citation: Eur J Pediatr. 2005 Jan;164(1):28-30
references.pmid: 15517377
references.citation: J Biol Chem. 2002 Jun 21;277(25):22147-55
references.pmid: 11940594
references.citation: Am J Respir Crit Care Med. 2002 May 1;165(9):1322-8
references.pmid: 11991887
references.citation: J Cell Biol. 2006 Jan 30;172(3):395-407
references.pmid: 16449190
references.citation: Pediatrics. 1995 Dec;96(6):1046-52
references.pmid: 7491219
references.citation: Pediatr Dev Pathol. 2000 Jul-Aug;3(4):335-45
references.pmid: 10890249
references.citation: J Biol Chem. 2007 Mar 30;282(13):9628-9634
references.pmid: 17267394
references.citation: J Clin Invest. 2002 Feb;109(4):475-80
references.pmid: 11854319
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L720-9
references.pmid: 17586700
references.citation: N Engl J Med. 1993 Feb 11;328(6):406-10
references.pmid: 8421459
references.citation: Ulster Med J. 2009 Jan;78(1):51-2
references.pmid: 19252731
references.citation: Am J Hum Genet. 2000 Jan;66(1):92-9
references.pmid: 10631139
references.citation: N Engl J Med. 2003 Dec 25;349(26):2527-39
references.pmid: 14695413
references.citation: J Exp Med. 1999 Sep 20;190(6):875-80
references.pmid: 10499925
references.citation: J Clin Invest. 1994 Apr;93(4):1860-3
references.pmid: 8163685
references.citation: Pediatr Res. 2005 Jan;57(1):89-98
references.pmid: 15557112
references.citation: N Engl J Med. 2004 Mar 25;350(13):1296-303
references.pmid: 15044640
references.citation: N Engl J Med. 2007 Mar 29;356(13):1317-26
references.pmid: 17392301
references.citation: J Biol Chem. 2006 Apr 7;281(14):9791-800
references.pmid: 16415354
references.citation: J Pediatr. 2002 Sep;141(3):426-8
references.pmid: 12219067
references.citation: Early Hum Dev. 2000 Feb;57(2):85-94
references.pmid: 10735455
references.citation: J Bioenerg Biomembr. 2001 Dec;33(6):475-9
references.pmid: 11804189
references.citation: Eur Respir J. 2004 Dec;24(6):1072-3
references.pmid: 15572558
references.citation: J Pediatr. 1994 Jan;124(1):125-8
references.pmid: 8283361
references.citation: Annu Rev Physiol. 2002;64:775-802
references.pmid: 11826288
references.citation: N Engl J Med. 2001 Feb 22;344(8):573-9
references.pmid: 11207353
references.citation: Chest. 2008 Jul;134(1):192-5
references.pmid: 18628224
references.citation: J Mol Biol. 2003 Jan 10;325(2):259-74
references.pmid: 12488094
references.citation: Eur Respir J. 2004 Jul;24(1):30-9
references.pmid: 15293602
references.citation: Pediatr Crit Care Med. 2006 Mar;7(2):177-9
references.pmid: 16474258
references.citation: J Pediatr. 1994 Apr;124(4):655
references.pmid: 8151487
references.citation: Neurogenetics. 2005 Dec;6(4):209-15
references.pmid: 16220345
references.citation: Pediatr Crit Care Med. 2008 Nov;9(6):e43-6
references.pmid: 18997591
references.citation: Am J Respir Cell Mol Biol. 2002 Oct;27(4):481-6
references.pmid: 12356582