title: Telomerase and idiopathic pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is the most common manifestation of telomere-mediated disorders. Germline mutations in the essential telomerase genes, hTERT and hTR, are the causal genetic defect in up to one-sixth of pulmonary fibrosis families. The presence of telomerase mutations in this subset is significant for clinical decisions as affected individuals can develop extra-pulmonary complications related to telomere shortening such as bone marrow failure and cryptogenic liver cirrhosis. There is also evidence that IPF is an ancestral manifestation of autosomal dominant telomere syndromes where, with successive generations, the disease evolves from pulmonary fibrosis into a bone marrow failure-predominant disorder, defining a unique form of genetic anticipation. Here I review the significance of telomere defects for understanding the genetics, disease patterns and pathophysiology of IPF. The importance of this diagnosis for patient care decisions will also be discussed.
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. marmani1@jhmi.edu
authors.forename: Mary
authors.initials: M
authors.lastname: Armanios
mesh_terms: D000367:Age Factors; D001855:Bone Marrow Diseases / Q000150:complications; D019871:Dyskeratosis Congenita / Q000235:genetics; D004646:Emphysema / Q000235:genetics; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006801:Humans; D011658:Pulmonary Fibrosis / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D059506:Telomere Shortening
chemical_list: D019098:Telomerase
references.citation: PLoS One. 2011 Mar 10;6(3):e17858
references.pmid: 21423765
references.citation: Blood. 2011 May 26;117(21):5607-11
references.pmid: 21436073
references.citation: J Med Genet. 2011 May;48(5):327-33
references.pmid: 21415081
references.citation: Proc Am Thorac Soc. 2006 Aug;3(6):503-10
references.pmid: 16921129
references.citation: Eur Respir J. 2005 Oct;26(4):586-93
references.pmid: 16204587
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15960-4
references.pmid: 16247010
references.citation: Br J Haematol. 2000 Sep;110(4):768-79
references.pmid: 11054058
references.citation: Blood. 2009 Jan 8;113(2):309-16
references.pmid: 18931339
references.citation: N Engl J Med. 2011 Mar 10;364(10):897-906
references.pmid: 21388308
references.citation: Blood. 2008 Nov 1;112(9):3594-600
references.pmid: 18669893
references.citation: Mol Cell Biol. 1999 Jan;19(1):567-76
references.pmid: 9858580
references.citation: Nat Genet. 1998 May;19(1):32-8
references.pmid: 9590285
references.citation: Pediatr Blood Cancer. 2009 Sep;53(3):520-3
references.pmid: 19415736
references.citation: Cell. 1985 Dec;43(2 Pt 1):405-13
references.pmid: 3907856
references.citation: Pediatr Transplant. 2007 Sep;11(6):584-94
references.pmid: 17663679
references.citation: Nature. 2001 Sep 27;413(6854):432-5
references.pmid: 11574891
references.citation: Am J Respir Crit Care Med. 2009 May 1;179(9):759-64
references.pmid: 19383929
references.citation: Am J Respir Crit Care Med. 2011 Oct 15;184(8):904-12
references.pmid: 21757622
references.citation: Nat Genet. 2004 May;36(5):447-9
references.pmid: 15098033
references.citation: Curr Biol. 2000 Nov 16;10(22):1459-62
references.pmid: 11102810
references.citation: PLoS Genet. 2011 Mar;7(3):e1001352
references.pmid: 21483807
references.citation: Mutat Res. 2012 Feb 1;730(1-2):3-11
references.pmid: 22093366
references.citation: Respir Med. 2010 Feb;104(2):305-9
references.pmid: 19782552
references.citation: Proc Natl Acad Sci U S A. 2007 May 1;104(18):7552-7
references.pmid: 17460043
references.citation: PLoS One. 2009 Nov 20;4(11):e7926
references.pmid: 19936245
references.citation: Am J Respir Crit Care Med. 2006 Oct 1;174(7):810-6
references.pmid: 16809633
references.citation: Mutat Res. 2012 Feb 1;730(1-2):68-74
references.pmid: 21600224
references.citation: Am J Respir Crit Care Med. 2008 Oct 1;178(7):729-37
references.pmid: 18635888
references.citation: Annu Rev Genomics Hum Genet. 2009;10:45-61
references.pmid: 19405848
references.citation: Bone Marrow Transplant. 2011 Jan;46(1):98-104
references.pmid: 20383216
references.citation: Am J Hum Genet. 2009 Dec;85(6):823-32
references.pmid: 19944403
references.citation: Cell. 2000 Mar 3;100(5):503-14
references.pmid: 10721988
references.citation: Nature. 1989 Jan 26;337(6205):331-7
references.pmid: 2463488
references.citation: Hum Mutat. 2009 Nov;30(11):1567-73
references.pmid: 19760749
references.citation: Am J Respir Crit Care Med. 2005 Nov 1;172(9):1146-52
references.pmid: 16109978
references.citation: Am J Respir Crit Care Med. 2002 Jan 15;165(2):277-304
references.pmid: 11790668
references.citation: Clin Genet. 2008 Feb;73(2):103-12
references.pmid: 18005359
references.citation: Cell. 1997 Oct 3;91(1):25-34
references.pmid: 9335332
references.citation: Nature. 1999 Dec 2;402(6761):551-5
references.pmid: 10591218
references.citation: Blood. 2003 Aug 1;102(3):916-8
references.pmid: 12676774
references.citation: Mutat Res. 2012 Feb 1;730(1-2):43-51
references.pmid: 21745483
references.citation: Cell. 1987 Dec 24;51(6):887-98
references.pmid: 3319189
references.citation: Trends Biochem Sci. 2004 Apr;29(4):183-92
references.pmid: 15082312
references.citation: N Engl J Med. 2005 Apr 7;352(14):1413-24
references.pmid: 15814878
references.citation: Am J Hum Genet. 2008 Feb;82(2):501-9
references.pmid: 18252230
references.citation: Mol Cell Biol. 2011 Jun;31(12):2369-79
references.pmid: 21464209
references.citation: Cell. 2005 Dec 16;123(6):1121-31
references.pmid: 16360040
references.citation: N Engl J Med. 2007 Mar 29;356(13):1317-26
references.pmid: 17392301
references.citation: Cell. 1999 Mar 5;96(5):701-12
references.pmid: 10089885
references.citation: PLoS One. 2010 May 19;5(5):e10680
references.pmid: 20502709
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13051-6
references.pmid: 18753630
references.citation: Respir Med. 2009 Jun;103(6):927-31
references.pmid: 19058956
references.citation: Am J Respir Cell Mol Biol. 2003 Sep;29(3 Suppl):S47-50
references.pmid: 14503554
references.citation: Bone Marrow Transplant. 2003 May;31(10):847-50
references.pmid: 12748659
references.citation: Nature. 1998 Apr 9;392(6676):569-74
references.pmid: 9560153
references.citation: Nat Rev Genet. 2010 Nov;11(11):786-99
references.pmid: 20953213