Universität zu Köln

Ralser, Damian J., Basmanav, F. Buket Ue., Tafazzoli, Aylar, Wititsuwannakul, Jade, Delker, Sarah, Danda, Sumita, Thiele, Holger, Wolf, Sabrina, Busch, Michelle, Pulimood, Susanne A., Altmueller, Janine, Nuernberg, Peter, Lacombe, Didier ORCID: 0000-0002-8956-2207, Hillen, Uwe, Wenzel, Joerg, Frank, Jorge, Odermatt, Benjamin and Betz, Regina C. (2017). Mutations in gamma-secretase subunit-encoding PSENEN underlie Dowling-Degos disease associated with acne inversa. J. Clin. Invest., 127 (4). S. 1485 - 1491. ANN ARBOR: AMER SOC CLINICAL INVESTIGATION INC. ISSN 1558-8238

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Abstract

Dowling-Degos disease (DDD) is an autosomal-dominant disorder of skin pigmentation associated with mutations in keratin 5 (KRT5), protein O-fucosyltransferase 1 (POFUT1), or protein O-glucosyltransferase 1 (POGLUT1). Here, we have identified 6 heterozygous truncating mutations in PSENEN, encoding presenilin enhancer protein 2, in 6 unrelated patients and families with DDD in whom mutations in KRT5, POFUT1, and POGLUT1 have been excluded. Further examination revealed that the histopathologic feature of follicular hyperkeratosis distinguished these 6 patients from previously studied individuals with DDD. Knockdown of psenen in zebrafish larvae resulted in a phenotype with scattered pigmentation that mimicked human DDD. In the developing zebrafish larvae, in vivo monitoring of pigment cells suggested that disturbances in melanocyte migration and differentiation underlie the DDD pathogenesis associated with PSENEN. Six of the PSENEN mutation carriers presented with comorbid acne inversa (AI), an inflammatory hair follicle disorder, and had a history of nicotine abuse and/or obesity, which are known trigger factors for AI. Previously, PSENEN mutations were identified in familial AI, and comanifestation of DDD and AI has been reported for decades. The present work suggests that PSENEN mutations can indeed cause a comanifestation of DDD and AI that is likely triggered by predisposing factors for AI. Thus, the present report describes a DDD subphenotype in PSENEN mutation carriers that is associated with increased susceptibility to AI.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ralser, Damian J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Basmanav, F. Buket Ue. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tafazzoli, Aylar UNSPECIFIED UNSPECIFIED UNSPECIFIED Wititsuwannakul, Jade UNSPECIFIED UNSPECIFIED UNSPECIFIED Delker, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Danda, Sumita UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Sabrina UNSPECIFIED UNSPECIFIED UNSPECIFIED Busch, Michelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Pulimood, Susanne A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Lacombe, Didier UNSPECIFIED orcid.org/0000-0002-8956-2207 UNSPECIFIED Hillen, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Wenzel, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Frank, Jorge UNSPECIFIED UNSPECIFIED UNSPECIFIED Odermatt, Benjamin UNSPECIFIED UNSPECIFIED UNSPECIFIED Betz, Regina C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-234166
DOI:	10.1172/JCI90667
Journal or Publication Title:	J. Clin. Invest.
Volume:	127
Number:	4
Page Range:	S. 1485 - 1491
Date:	2017
Publisher:	AMER SOC CLINICAL INVESTIGATION INC
Place of Publication:	ANN ARBOR
ISSN:	1558-8238
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HIDRADENITIS SUPPURATIVA Multiple languages Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23416