• English
    • العربية
  • العربية
  • Login
  • QU
  • QU Library
  •  Home
  • Communities & Collections
  • Help
    • Item Submission
    • Publisher policies
    • User guides
    • FAQs
  • About QSpace
    • Vision & Mission
    • QSpace policies
View Item 
  •   Qatar University Digital Hub
  • Qatar University Institutional Repository
  • Academic
  • Faculty Contributions
  • College of Arts & Sciences
  • Biological & Environmental Sciences
  • View Item
  • Qatar University Digital Hub
  • Qatar University Institutional Repository
  • Academic
  • Faculty Contributions
  • College of Arts & Sciences
  • Biological & Environmental Sciences
  • View Item
  •      
  •  
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    A rare loss-of-function genetic mutation suggest a role of dermcidin deficiency in hidradenitis suppurativa pathogenesis

    Thumbnail
    View/Open
    HS_dermicidin (5.364Mb)
    Date
    2022-12-05
    Author
    Tricarico, Paola Maura
    Gratton, Rossella
    Santos-Silva, Carlos André dos
    Moura, Ronald Rodrigues de
    Ura, Blendi
    Sommella, Eduardo
    Campiglia, Pietro
    Del Vecchio, Cecilia
    Moltrasio, Chiara
    Berti, Irene
    D’Adamo, Adamo Pio
    Elsherbini, Ahmed M.A.
    Staudenmaier, Lena
    Chersi, Karin
    Boniotto, Michele
    Krismer, Bernhard
    Schittek, Birgit
    Crovella, Sergio
    ...show more authors ...show less authors
    Metadata
    Show full item record
    Abstract
    Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a multifactorial aetiology that involves a strict interplay between genetic factors, immune dysregulation and lifestyle. Familial forms represent around 40% of total HS cases and show an autosomal dominant mode of inheritance of the disease. In this study, we conducted a whole-exome sequence analysis on an Italian family of 4 members encompassing a vertical transmission of HS. Focusing on rare damaging variants, we identified a rare insertion of one nucleotide (c.225dupA:p.A76Sfs*21) in the DCD gene encoding for the antimicrobial peptide dermcidin (DCD) that was shared by the proband, his affected father and his 11-years old daughter. Since several transcriptome studies have shown a significantly decreased expression of DCD in HS skin, we hypothesised that the identified frameshift insertion was a loss-of-function mutation that might be associated with HS susceptibility in this family. We thus confirmed by mass spectrometry that DCD levels were diminished in the affected members and showed that the antimicrobial activity of a synthetic DCD peptide resulting from the frameshift mutation was impaired. In order to define the consequences related to a decrease in DCD activity, skin microbiome analyses of different body sites were performed by comparing DCD mutant and wild type samples, and results highlighted significant differences between the groins of mutated and wild type groups. Starting from genetic analysis conducted on an HS family, our findings showed, confirming previous transcriptome results, the potential role of the antimicrobial DCD peptide as an actor playing a crucial part in the etio-pathogenesis of HS and in the maintenance of the skin’s physiological microbiome composition; so, we can hypothesise that DCD could be used as a novel target for personalised therapeutic approach.
    URI
    https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85144185023&origin=inward
    DOI/handle
    http://dx.doi.org/10.3389/fimmu.2022.1060547
    http://hdl.handle.net/10576/37576
    Collections
    • Biological & Environmental Sciences [‎661‎ items ]

    entitlement


    Qatar University Digital Hub is a digital collection operated and maintained by the Qatar University Library and supported by the ITS department

    Contact Us | Send Feedback
    Contact Us | Send Feedback | QU

     

     

    Home

    Submit your QU affiliated work

    Browse

    All of Digital Hub
      Communities & Collections Publication Date Author Title Subject Type Language Publisher
    This Collection
      Publication Date Author Title Subject Type Language Publisher

    My Account

    Login

    Statistics

    View Usage Statistics

    About QSpace

    Vision & Mission QSpace policies

    Help

    Item Submission Publisher policiesUser guides FAQs

    Qatar University Digital Hub is a digital collection operated and maintained by the Qatar University Library and supported by the ITS department

    Contact Us | Send Feedback
    Contact Us | Send Feedback | QU

     

     

    Video