TY - JOUR
T1 - Telomerase and idiopathic pulmonary fibrosis
AU - Armanios, Mary
N1 - Funding Information:
I am grateful for critical comments from lab members, and help with the illustrations from Jennifer Fairman. Work in my lab is supported by the United States National Institutes of Health , the Maryland Stem Cell Research Foundation and the Flight Attendants Medical Research Institute .
PY - 2012/2/1
Y1 - 2012/2/1
N2 - 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.
AB - 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.
KW - Aplastic anemia
KW - Diabetes
KW - Dyskeratosis congenita
KW - Emphysema
KW - Interstitial lung disease
KW - Liver cirrhosis
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U2 - 10.1016/j.mrfmmm.2011.10.013
DO - 10.1016/j.mrfmmm.2011.10.013
M3 - Review article
C2 - 22079513
AN - SCOPUS:84855473741
SN - 0027-5107
VL - 730
SP - 52
EP - 58
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -