Altered keratinization and vitamin D metabolism may be key pathogenetic pathways in syndromic hidradenitis suppurativa: a novel whole exome sequencing approach.

Abstract

BACKGROUND:

Diagnosis of pyoderma gangrenosum, acne and hidradenitis suppurativa (PASH) and pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) patients, in spite of recently identified genetic variations, is just clinical, since most patients do not share the same mutations, and the mutations themselves are not informative of the biological pathways commonly disrupted in these patients.

OBJECTIVE:

To reveal genetic changes more closely related to PASH and PAPASH etiopathogenesis, identifying novel common pathways involved in these diseases.

METHODS:

Cohort study on PASH (n = 4) and PAPASH (n = 1) patients conducted using whole exome sequencing (WES) approach and a novel bioinformatic pipeline aimed at discovering potentially candidate genes selected from density mutations and involved in pathways relevant to the disease.

RESULTS:

WES results showed that patients presented 90 genes carrying mutations with deleterious and/or damage impact: 12 genes were in common among the 5 patients and bared 237 ns ExonVar (54 and 183 in homozygosis and heterozygosis, respectively). In the pathway enrichment analysis, only 10 genes were included, allowing us to retrieve 4 pathways shared by all patients: (1) Vitamin D metabolism, (2) keratinization, (3) formation of the cornified envelope and (4) steroid metabolism. Interestingly, all patients had vitamin D levels lower than normal, with a mean value of 10 ng/mL.

CONCLUSION:

Our findings, through a novel strategy for analysing the genetic background of syndromic HS patients, suggested that vitamin D metabolism dysfunctions seem to be crucial in PASH and PAPASH pathogenesis. Based on low vitamin D serum levels, its supplementation is envisaged.

• Authors: Lucas Brandao, Ronald Moura, Paola Maura Tricarico, Rossella Gratton, Giovanni Genovese, Chiara Moltrasio, Simone Garcovich, Michele Boniotto, Sergio Crovella, Angelo Valerio Marzano
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 99 Issue 1 Pg. 17-22 (Jul 2020) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 32518053 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Vitamin D

Topics

• Acne Vulgaris (diagnosis, genetics, metabolism, pathology)
• Adolescent
• Adult
• Arthritis, Infectious (diagnosis, genetics, metabolism, pathology)
• Computational Biology
• Female
• Follow-Up Studies
• Hidradenitis Suppurativa (diagnosis, genetics, metabolism, pathology)
• Humans
• Keratinocytes (pathology)
• Male
• Pyoderma Gangrenosum (diagnosis, genetics, metabolism, pathology)
• Skin (cytology, pathology)
• Syndrome
• Vitamin D (metabolism)
• Exome Sequencing
• Young Adult