• Am. J. Respir. Crit. Care Med. · Mar 2015

    Rare Variants in RTEL1 are Associated with Familial Interstitial Pneumonia.

    • Joy D Cogan, Jonathan A Kropski, Min Zhao, Daphne B Mitchell, Lynette Rives, Cheryl Markin, Errine T Garnett, Keri H Montgomery, Wendi R Mason, David F McKean, Julia Powers, Elissa Murphy, Lana M Olson, Leena Choi, Dong-Sheng Cheng, Elizabeth Marchani Blue, Lisa R Young, Lisa H Lancaster, Mark P Steele, Kevin K Brown, Marvin I Schwarz, Tasha E Fingerlin, David A Schwartz, William E Lawson, James E Loyd, Zhongming Zhao, John A Phillips, and Timothy S Blackwell.
    • 1 Division of Medical Genetics and Genomic Medicine, Department of Pediatrics.
    • Am. J. Respir. Crit. Care Med. 2015 Mar 15; 191 (6): 646655646-55.

    RationaleUp to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families.ObjectivesTo determine if new disease-causing rare genetic variants could be identified using whole-exome sequencing of affected members from FIP families, providing additional insights into disease pathogenesis.MethodsAffected subjects from 25 kindreds were selected from an ongoing FIP registry for whole-exome sequencing from genomic DNA. Candidate rare variants were confirmed by Sanger sequencing, and cosegregation analysis was performed in families, followed by additional sequencing of affected individuals from another 163 kindreds.Measurements And Main ResultsWe identified a potentially damaging rare variant in the gene encoding for regulator of telomere elongation helicase 1 (RTEL1) that segregated with disease and was associated with very short telomeres in peripheral blood mononuclear cells in 1 of 25 families in our original whole-exome sequencing cohort. Evaluation of affected individuals in 163 additional kindreds revealed another eight families (4.7%) with heterozygous rare variants in RTEL1 that segregated with clinical FIP. Probands and unaffected carriers of these rare variants had short telomeres (<10% for age) in peripheral blood mononuclear cells and increased T-circle formation, suggesting impaired RTEL1 function.ConclusionsRare loss-of-function variants in RTEL1 represent a newly defined genetic predisposition for FIP, supporting the importance of telomere-related pathways in pulmonary fibrosis.

      Pubmed     Free full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…

Want more great medical articles?

Keep up to date with a free trial of metajournal, personalized for your practice.
1,706,642 articles already indexed!

We guarantee your privacy. Your email address will not be shared.