Theut Riis, Peter, Loft , Isabella C, Yazdanyar, Shiva, Kjærsgaard Andersen, Rune, Pedersen, Ole B, Ring, Hans Christian, Huber, Roland, Sultan , Marc, Loesche, Christian, Saunte, Ditte ML and Jemec, Gregor BE (2021) Full exome sequencing of 11 families with Hidradenitis suppurativa. Full exome sequencing of 11 families with Hidradenitis suppurativa. , 35 (5). pp. 1203-1211. ISSN 0926-9959 , 1468-3083

Abstract

Importance: Hidradenitis Suppurativa (HS) is not a well-studied or easily treated disease. Genetic information is essential for advances in the understanding and treatment of HS.
Objective: This study aims to examine mutations in the gamma-secretase complex, the Notch signaling pathway and to perform a Mendelian analysis of genetic variants that segregated with disease in a full exome sequencing of 11 families with HS.
Design: Whole exome sequencing and Mendelian analysis of 11 families with HS from Denmark.
Setting: Single-centre tertiary level clinic.
Participants: Patients with a clinical diagnosis of active HS and a positive family history of HS, were recruited. Consenting family members were enrolled and examined for HS as well. We included 11 families, with a total of 51 participants, 24 with HS and 27 without.
Intervention(s) (for clinical trials) or Exposure(s) (for observational studies): Whole exome sequencing using HiSeq platform as paired-end 2 x 150 bases, targeting 80x coverage.
Main Outcome(s) and Measure(s): We report mutations in genes in gamma-secretase and Notch pathway. As well as mutations perfectly segregated with the disease.
Results: We found mutations in the Notch pathway for all families, but only mutations in the PSENEN and APH1B of the gamma-secretase genes. We also report 161 variants of unknown significance that segregated with the disease within these families.
Conclusions and Relevance: We did not find causative mutation for each family in this study, supporting the theory that HS is rarely caused by single-gene mutations. We suggest that future genetic studies should be focused on genome-wide association with thousands of cases, as this technique is much better suited for suspected polygenic diseases

Item Type:	Article
Date Deposited:	21 Oct 2021 00:45
Last Modified:	21 Oct 2021 00:45
URI:	https://oak.novartis.com/id/eprint/42552