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British Journal of Dermatology

A phenotype combining hidradenitis suppurativa with Dowling- Degos disease caused by a founder mutation in PSENEN. Mor Pavlovsky , Ofer Sarig, Marina Eskin-Schwartz, Natalya Malchin , Ron Bochner, Janan Mohamad , Andrea Gat, Alon Peled, Ariela Hafner , Eli Sprecher.

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British Journal of Dermatology

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  1. A phenotype combining hidradenitissuppurativa with Dowling-Degos disease caused by a founder mutation in PSENEN. Mor Pavlovsky, Ofer Sarig, Marina Eskin-Schwartz, Natalya Malchin, Ron Bochner, JananMohamad, Andrea Gat, Alon Peled, Ariela Hafner, Eli Sprecher British Journal of Dermatology Department of Dermatology and Institute of Pathology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

  2. Dr MorPavlovksy

  3. Introduction DDD and HS share important clinical features including: • Autosomal dominant inheritance • Onset during puberty • Flexural location • Hair follicle involvement

  4. ADAM 10 NOTCH NOTCH POGLUT1 Kitamura Dowling Degos EBS KRT5 POFUT1 Gali Gali Dowling Degos Poliferation & pigmentation Proliferation & pigmentation Betz et al, Am J Hum Genet, 2006, Sprecher et al, Br J Dermatol, 2007; Li et al, Am J Hum Genet, 2013; Basmanv et al, Am J Hum Genet, 2014; Kono et al, Hum Mol genet, 2013

  5. ADAM 10 NOTCH NCSTN PS1 NOTCH POGLUT1 Kitamura PSENEN APH1 Dowling Degos EBS KRT5 g-secretase POFUT1 Gali Gali Dowling Degos Proliferation & pigmentation Wang et al, Science, 2010; Pink et al, J Invest Dermatol, 2013

  6. Methods • Four patients with a combination of DDD and HS • Sanger sequencing of PSENEN gene • Microsatellite analysis • qRT-PCR • Notch luciferase reporter construct

  7. Results – A novel mutation in PSENEN gene WT/WT WT/c.168T>G

  8. Results – Microsatellite analysis

  9. Results – Gene expression analysis

  10. Results -Notch luciferase reporter construct two sided t-test; ***p<0.001

  11. Discussion • Notch signaling has been shown to regulate differentiation of the interfollicular epithelium and hair follicles • Notch pathway contributes to the regulation of melanocyte homeostasis • Abnormal Notch signaling underlies the phenotypic manifestations of both HS and DDD

  12. Conclusions HS-DDD can be added to other disorders that are the result of abnormal Notch signaling

  13. Please insert photograph / photographs of research team

  14. Call for correspondence • Why not join the debate on this article through our correspondence section? • Rapid responses should not exceed 350 words, four references and one figure • Further details can be found here

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