Publication:
Investigation of gamma secretase gene complex mutations in German population with Hidradenitis suppurativa designate a complex polygenic heritage

dc.contributor.coauthorBaumgartner, M.
dc.contributor.coauthorLichtner, P.
dc.contributor.coauthorEckstein, G.
dc.contributor.coauthorHariry, H.
dc.contributor.coauthorChen, W. C.
dc.contributor.coauthorRuzicka, T.
dc.contributor.coauthorMelnik, B.
dc.contributor.coauthorPlewig, G.
dc.contributor.coauthorWagner, M.
dc.contributor.coauthorGiehl, K. A.
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorVural, Seçil
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-11-09T23:13:43Z
dc.date.issued2021
dc.description.abstractBackground: Hidradenitis suppurativa (HS) is a chronic inflammatory disease affecting apocrine gland-bearing skin in the axilla, groin and under the breasts. Mutations of the gamma secretase gene complex, which is essential in the activation of Notch signalling pathways, were shown in some families with HS and in a few sporadic cases. Although an imbalance in Notch signalling is implicated in the pathogenesis, the exact mechanism of HS development is yet unknown. Objectives: We aim to investigate the genetic basis of HS by determining the presence of mutations of gamma secretase gene complex in a cohort of HS patients and by searching for a disease-causing pathogenic variant in a multi-generational HS family using parametric linkage analysis. Methods: Thirty-eight patients clinically diagnosed with HS were included in this study. All exons and exon-intron boundaries of the genes encoding gamma secretase complex consisting of six genes: APH1A, APH1B, PSENEN, NCSTN, PSEN1 and PSEN2 were sequenced by Sanger technique. Genetic mapping with parametric linkage analysis for the patients in the family was performed with eight affected and four healthy individuals. The logarithm of odds was calculated. Results: In a sporadic patient with early-onset, severe lesions in axilla and groin, a novel single-nucleotide deletion causing frameshift in exon 1 of the NCSTN gene was identified ((NM_015331.3): c.38delG, p.(Gly13Glufs*15)). The LOD score of 1.5 was never exceeded in any region of the genome, pointing towards intricate multi-genic inheritance pattern within the affected family. Conclusions: The gamma secretase gene complex mutations were rare in our cohort (3.2%). Besides, our analysis indicates a possible complex multi-genic inheritance in a seemingly autosomal dominantly inherited large HS family. Genetics of both familial and sporadic HS may be complicated in most cases, and the role of other potential genes such as autoinflammatory and modifier genes as well as environmental factors may influence the pathogenesis.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue6
dc.description.openaccessNO
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.volume35
dc.identifier.doi10.1111/jdv.17163
dc.identifier.eissn1468-3083
dc.identifier.issn0926-9959
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85101869324
dc.identifier.urihttps://doi.org/10.1111/jdv.17163
dc.identifier.urihttps://hdl.handle.net/20.500.14288/10034
dc.identifier.wos624017300001
dc.keywordsGamma secretase gene complex mutations
dc.keywordsHidradenitis suppurativa designate
dc.keywordsPolygenic heritage
dc.language.isoeng
dc.publisherWiley
dc.relation.ispartofJournal of the European Academy of Dermatology and Venereology
dc.subjectDermatology
dc.titleInvestigation of gamma secretase gene complex mutations in German population with Hidradenitis suppurativa designate a complex polygenic heritage
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorVural, Seçil
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit2School of Medicine
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