Citations 2
Darier disease—A review highlighting new insights from the Darier Disease International Task Force
Labbouz, Sofia , Xiong, Grace , Murrell, Dedee Frances, Mueller, Simon M. , Mohandesi, Nessa Aghazadeh, Aldhaheri, Ahmed Salem, Asayag, Nissim, Baselga, Eulalia, Nadler, Chen , Chu, Chia‐Yu , Edminister, John R. , Guenova, Emmanuella, Gönülal, Melis , Gostynski, Antoni, Gupta, Lalit Kumar, Mazereeuw‐Hautier, Juliette, Hoetzenecker, Wolfram , Itin, Peter, Jankowski, Marek , Medvecz, Márta, Moosbrugger‐Martinz, Verena , Paller, Amy S., Plázár, Dóra , Queiróz, Amadeu José Rodrigues , Riera‐Monroig, Josep , Rosa, Ralph, Schmuth, Matthias, Freire, Maella Severino , Shabat, Itzhak, Shapiro, Jonathan , Soto‐García, Diego , Stratigos, Alexander J., Tadini, Gianluca Abel, Takeichi, Takuya , Verma, Kaushal K. , Wikström, Jakob D. , Ziv, Michael , Dodiuk‐Gad, Roni Pircha, Xiong, Grace , Mueller, Simon M , Ezzedine, Khaled , Choate, Keith , Gostynski, Antoni , Gupta, Ankan , Hoetzenecker, Wolfram , Jankowski, Marek , Kubo, Akiharu , Lee, Haur Yueh , Lehman, Julia Scott, Mellerio, Jemima E , Queiróz, Amadeu José Rodrigues , Freire, Maella Severino , Shapiro, Jonathan , Soto-García, Diego , Takeichi, Takuya , Wikström, Jakob D , Zink, Alexander , Navarini, Alexander , Hovnanian, Alain , Murrell, D F , Aghazadeh, Nessa , Aldhaheri, Ahmed S., Guenova, Emmanuella , Gönülal, Melis , Mazereeuw‐Hautier, J. , Lehman, Julia S. , Lepekhova, Anfisa A. , Medvecz, Márta, Paller, Amy S. , Schmuth, Matthias , Simpson, Cory L. , Tadini, Gianluca , Wikström, Jakob D. , Dodiuk‐Gad, Roni P.
Journal of the European Academy of Dermatology and Venereology | June 1, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Darier disease (DD) is a rare autosomal dominant genodermatosis. This comprehensive review, developed by the Darier Disease International Task Force (DDITF), consolidates current knowledge on the genetic basis, molecular pathophysiology, clinical presentation, diagnosis and management of DD, offering a global perspective that unites shared expertise. The disease arises from pathogenic variants in the ATP2A2 gene, which encodes sarco/endoplasmic reticulum Ca 2+ ‐ATPase isoform 2 (SERCA2), leading to disrupted calcium homeostasis and impaired desmosomal integrity. Clinically, DD is classified based on lesion type (classic vs. non‐classic) and is often accompanied by significant extracutaneous manifestations. Management remains challenging and requires a multifaceted approach, including topical therapies, systemic retinoids and lifestyle modifications. Emerging treatments that target the underlying molecular mechanisms offer promise for improved outcomes. This review aims to provide an updated reference and practical guidance for clinicians involved in the care and study of DD.
Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca2+ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease
Cornatzer, Eric, Cornatzer, W. E., Shin, Dong Min , Pittelkow, Mark R. , Hovnanian, Alain , Ambudkar, Indu S. , Singh, Brij B. , Pani, Biswaranjan , Hovnanian, Alain
Molecular Biology of the Cell | August 10, 2006 | Volume: 17 | Issue: 10 | Pages: 4446-4458
The mechanism(s) involved in regulation of store operated calcium entry in Darier's disease (DD) is not known. We investigated the distribution and function of transient receptor potential canonical (TRPC) in epidermal skin cells. DD patients demonstrated up-regulation of TRPC1, but not TRPC3, in the squamous layers. Ca2+influx was significantly higher in keratinocytes obtained from DD patients and showed enhanced proliferation compared with normal keratinocytes. Similar up-regulation of TRPC1 was also detected in epidermal layers of SERCA2+/−mice. HaCaT cells expressed TRPC1 in the plasma membrane. Expression of sarco(endo)plasmic reticulum Ca2+ATPase (SERCA)2 small interfering RNA (siRNA) in HaCaT cells increased TRPC1 levels and thapsigargin-stimulated Ca2+influx, which was blocked by store-operated calcium entry inhibitors. Thapsigargin-stimulated intracellular Ca2+release was decreased in DD cells. DD keratinocytes exhibited increased cell survival upon thapsigargin treatment. Alternatively, overexpression of TRPC1 or SERCA2-siRNA in HaCaT cells demonstrated resistance to thapsigargin-induced apoptosis. These effects were dependent on external Ca2+and activation of nuclear factor-κB. Isotretinoin reduced Ca2+entry in HaCaT cells and decreased survival of HaCaT and DD keratinocytes. These findings put forward a novel consequence of compromised SERCA2 function in DD wherein up-regulation of TRPC1 augments cell proliferation and restrict apoptosis. We suggest that the anti-apoptotic effect of TRPC1 could potentially contribute to abnormal keratosis in DD.