• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2019
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2019
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    An atypical pulmonary fibrosis is associated with co-inheritance of mutations in the calcium binding protein genes S100A3 and S100A13

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Author
    Al-Mutairy, E.A.
    Luzina, I.G.
    Al-Mohanna, F.
    Date
    2019
    Journal
    The European respiratory journal
    Publisher
    European Respiratory Society
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://www.doi.org/10.1183/13993003.02041-2018
    Abstract
    BACKGROUND: Pulmonary fibrosis is one of the leading indications for lung transplantation. The disease, which is of unknown aetiology, can be progressive, resulting in distortion of the extracellular matrix (ECM), inflammation, fibrosis and eventual death. METHODS: 13 patients born to consanguineous parents from two unrelated families presenting with interstitial lung disease were clinically investigated. Nine patients developed respiratory failure and subsequently died. Molecular genetic investigations were performed on patients' whole blood or archived tissues, and cell biological investigations were performed on patient-derived fibroblasts. RESULTS: The combination of a unique pattern of early-onset lung fibrosis (at 12-15?years old) with distinctive radiological findings, including 1) traction bronchiectasis, 2) intralobular septal thickening, 3) shrinkage of the secondary pulmonary lobules mainly around the bronchovascular bundles and 4) early type 2 respiratory failure (elevated blood carbon dioxide levels), represents a novel clinical subtype of familial pulmonary fibrosis. Molecular genetic investigation of families revealed a hypomorphic variant in S100A3 and a novel truncating mutation in S100A13, both segregating with the disease in an autosomal recessive manner. Family members that were either heterozygous carriers or wild-type normal for both variants were unaffected. Analysis of patient-derived fibroblasts demonstrated significantly reduced S100A3 and S100A13 expression. Further analysis demonstrated aberrant intracellular calcium homeostasis, mitochondrial dysregulation and differential expression of ECM components. CONCLUSION: Our data demonstrate that digenic inheritance of mutations in S100A3 and S100A13 underlie the pathophysiology of pulmonary fibrosis associated with a significant reduction of both proteins, which suggests a calcium-dependent therapeutic approach for management of the disease.
    Keyword
    S100A3
    S100A13
    Pulmonary Fibrosis--genetics
    Pulmonary Fibrosis--physiopathology
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85070115794&doi=10.1183%2f13993003.02041-2018&partnerID=40&md5=796d8358493a0f2be8ce9eb4f7412ca1; http://hdl.handle.net/10713/10338
    ae974a485f413a2113503eed53cd6c53
    10.1183/13993003.02041-2018
    Scopus Count
    Collections
    UMB Open Access Articles 2019

    entitlement

    Related articles

    • Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations.
    • Authors: Diaz de Leon A, Cronkhite JT, Katzenstein AL, Godwin JD, Raghu G, Glazer CS, Rosenblatt RL, Girod CE, Garrity ER, Xing C, Garcia CK
    • Issue date: 2010 May 19
    • Novel genetic variant of HPS1 gene in Hermansky-Pudlak syndrome with fulminant progression of pulmonary fibrosis: a case report.
    • Authors: Doubková M, Trizuljak J, Vrzalová Z, Hrazdirová A, Blaháková I, Radová L, Pospíšilová Š, Doubek M
    • Issue date: 2019 Oct 16
    • Surfactant protein C mutations are the basis of a significant portion of adult familial pulmonary fibrosis in a dutch cohort.
    • Authors: van Moorsel CH, van Oosterhout MF, Barlo NP, de Jong PA, van der Vis JJ, Ruven HJ, van Es HW, van den Bosch JM, Grutters JC
    • Issue date: 2010 Dec 1
    • A large kindred of pulmonary fibrosis associated with a novel ABCA3 gene variant.
    • Authors: Campo I, Zorzetto M, Mariani F, Kadija Z, Morbini P, Dore R, Kaltenborn E, Frixel S, Zarbock R, Liebisch G, Hegermann J, Wrede C, Griese M, Luisetti M
    • Issue date: 2014 Apr 15
    • COL4A4-related nephropathy caused by a novel mutation in a large consanguineous Saudi family.
    • Authors: Ramzan K, Imtiaz F, Taibah K, Alnufiee S, Akhtar M, Al-Hazzaa SA, Al-Owain M
    • Issue date: 2014 Mar
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.