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Rare Filaggrin Variants Are Associated with Pustular Skin Diseases in Asians.

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  • معلومة اضافية
    • المصدر:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • الموضوع:
      Filaggrin Proteins* ; Intermediate Filament Proteins*/genetics ; Polymorphism, Single Nucleotide* ; Asian People*/genetics; Humans ; Female ; Male ; Adult ; Middle Aged ; Exome Sequencing ; Genetic Predisposition to Disease ; Psoriasis/genetics ; Psoriasis/pathology ; Aged ; Interferon-gamma/genetics ; Interferon-gamma/metabolism ; Autoantibodies/immunology ; Skin/pathology ; Skin/metabolism
    • نبذة مختصرة :
      Reactive pustular eruptions (RPEs) can manifest in a variety of conditions, including pustular psoriasis (PP) and adult-onset immunodeficiency syndrome due to anti-interferon-γ autoantibody (AOID). These RPEs can be attributed to different causes, one of which is genetic factors. However, the genetic basis for pustular skin diseases remains poorly understood. In our study, we conducted whole-exome sequencing on a cohort of 17 AOID patients with pustular reactions (AOID-PR) and 24 PP patients. We found that 76% and 58% of the AOID-PR and PP patients, respectively, carried rare genetic variations within the filaggrin (FLG) gene family. A total of 12 out of 21 SNPs on FLG had previously received clinical classifications, with only p.Ser2706Ter classified as pathogenic. In contrast, none of the FLG3 SNPs identified in this study had prior clinical classifications. Overall, these variations had not been previously documented in cases of pustular disorders, and two of them were entirely novel discoveries. Immunohistochemical analysis of skin biopsies revealed that FLG variants like p.Ser860Trp, p.Gly3903Ter, p.Gly2440Glu, and p.Glu2133Asp caused reductions in FLG levels similar to the pathogenic FLG p.Ser2706Ter. These results highlight rare FLG variants as potential novel genetic risk factors contributing to pustule formation in both AOID and PP.
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    • Grant Information:
      TGCMU2566P011/2566 Chiang Mai University; Health System Research Institute; 001/2565 Chiang Mai University Faculty of Medicine Research Fund
    • Contributed Indexing:
      Keywords: AOID; filaggrin; pustular psoriasis; reactive pustular eruptions; whole-exome sequencing
    • الرقم المعرف:
      0 (Filaggrin Proteins)
      0 (FLG protein, human)
      0 (Intermediate Filament Proteins)
      82115-62-6 (Interferon-gamma)
      0 (Autoantibodies)
    • الموضوع:
      Date Created: 20240627 Date Completed: 20240627 Latest Revision: 20240629
    • الموضوع:
      20240629
    • الرقم المعرف:
      PMC11203790
    • الرقم المعرف:
      10.3390/ijms25126466
    • الرقم المعرف:
      38928170