@article{82b7925b27944f19a558bc445387a96b,
title = "Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening",
abstract = "Idiopathic pulmonary fibrosis (IPF) is an age-related disease featuring progressive lung scarring. To elucidate the molecular basis of IPF, we performed exome sequencing of familial kindreds with pulmonary fibrosis. Gene burden analysis comparing 78 European cases and 2,816 controls implicated PARN, an exoribonuclease with no previous connection to telomere biology or disease, with five new heterozygous damaging mutations in unrelated cases and none in controls (P = 1.3 × 10 -8); mutations were shared by all affected relatives (odds in favor of linkage = 4,096:1). RTEL1, an established locus for dyskeratosis congenita, harbored significantly more new damaging and missense variants at conserved residues in cases than in controls (P = 1.6 × 10 -6). PARN and RTEL1 mutation carriers had shortened leukocyte telomere lengths, and we observed epigenetic inheritance of short telomeres in family members. Together, these genes explain {\^a} 1/47% of familial pulmonary fibrosis and strengthen the link between lung fibrosis and telomere dysfunction.",
author = "Stuart, {Bridget D.} and Jungmin Choi and Samir Zaidi and Chao Xing and Brody Holohan and Rui Chen and Mihwa Choi and Pooja Dharwadkar and Fernando Torres and Girod, {Carlos E.} and Jonathan Weissler and John Fitzgerald and Corey Kershaw and Julia Klesney-Tait and Yolanda Mageto and Shay, {Jerry W.} and Weizhen Ji and Kaya Bilguvar and Shrikant Mane and Lifton, {Richard P.} and Garcia, {Christine Kim}",
note = "Funding Information: We are grateful to the probands and their families for their participation, to A. Young for technical excellence, to S. Nolasco, K. Stephens and G. Wools for their help with blood sample collections, to the Yale Center for Genome Analysis for the generation of exome sequence data, and to the Yale Center for Genome Analysis and the McDermott Center Bioinformatics Core for sequence analysis. The authors acknowledge funding support from the following sources: US National Institutes of Health (NIH) National Center for Advancing Translational Sciences grant UL1TR001105; US NIH grant U54HG006504 (to the Yale Center for Mendelian Genomics); the Howard Hughes Medical Institute (R.P.L.); US NIH grant K12HD068369 (B.D.S.); and US NIH grant R01HL093096 (C.K.G.). Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",
year = "2015",
month = may,
day = "30",
doi = "10.1038/ng.3278",
language = "English",
volume = "47",
pages = "512--517",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "5",
}