The genetic basis for most patients with pustular skin disease remains elusive

Mössner R, Wilsmann-Theis D, Oji V, Gkogkolou P, Löhr S, Schulz P, Körber A, Prinz JC, Renner R, Schäkel K, Vogelsang L, Peters KP, Philipp S, Reich K, Ständer H, Jacobi A, Weyergraf A, Kingo K, Kõks S, Gerdes S, Steinz K, Schill T, Griewank KG, Müller M, Frey S, Ebertsch L, Uebe S, Sticherling M, Sticht H, Hüffmeier U (2017)

Publication Type: Journal article

Publication year: 2017

Journal

DOI: 10.1111/bjd.15867

Abstract

Rare variants in the genes IL36RN, CARD14 and AP1S3 have been identified to cause/ contribute to pustular skin diseases, primarily generalized pustular psoriasis (GPP).To better understand the disease-relevance of these genes, we screened our cohorts of patients with pustular skin diseases (primarily GPP and palmoplantar pustular psoriasis [PPP]) for coding changes in these three genes. Carriers of single heterozygous IL36RN mutations were screened for a second mutation in IL36RN.Coding exons of IL36RN, CARD14 and AP1S3 were sequenced in 67 patients - 61 with GPP, 2 with acute generalized exanthematous pustulosis and 4 with acrodermatitis continua suppurativa Hallopeau. We screened IL36RN and AP1S3 for intragenic copy-number-variants, 258 PPP patients for coding changes in AP1S3. 11 heterozygous IL36RN mutations carriers were analyzed for a 2(nd) non-coding IL36RN mutation. Genotype-phenotype-correlations in carriers/ non-carriers of IL36RN mutations were assessed within the GPP cohort.The majority of patients (GPP:64%) did not carry rare variants in any of the three genes. Bi-allelic and mono-allelic IL36RN mutations were identified in 15 and 5 GPP patients, respectively. Non-coding rare IL36RN variants were not identified in heterozygous carriers. The only significant genotype-phenotype-correlation observed for IL36RN mutation carriers was early age of disease onset. Additional rare CARD14 or AP1S3 variants were identified in 15% of IL36RN mutations carriers.The identification of IL36RN mutation carriers harboring additional rare variants in CARD14 or AP1S3, indicates a more complex mode of inheritance of pustular psoriasis. Our results suggest additional disease-causing genetic factors in heterozygous IL36RN mutation carriers outside IL36RN. This article is protected by copyright. All rights reserved.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Heidelberg Germany (DE) Klinikum Bayreuth Germany (DE) Deutsches Zentrum für Diabetesforschung e.V. (DZD) Germany (DE) Klinikum Dortmund Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Fachklinik Bad Bentheim Germany (DE) University of Tartu Estonia (EE) Christian-Albrechts-Universität zu Kiel Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Universität Duisburg-Essen (UDE) Germany (DE) Georg-August-Universität Göttingen Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) Ludwig-Maximilians-Universität (LMU) Germany (DE)

How to cite

APA:

Mössner, R., Wilsmann-Theis, D., Oji, V., Gkogkolou, P., Löhr, S., Schulz, P.,... Hüffmeier, U. (2017). The genetic basis for most patients with pustular skin disease remains elusive. British Journal of Dermatology. https://dx.doi.org/10.1111/bjd.15867

MLA:

Mössner, R., et al. "The genetic basis for most patients with pustular skin disease remains elusive." British Journal of Dermatology (2017).

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