Autosomal-Dominant Calcium ATPase Disorders

1Department of Dermatology, University of Pécs, Pécs, Hungary.
Journal of Investigative Dermatology (Impact Factor: 7.22). 12/2006; 126(11):2370-6. DOI: 10.1038/sj.jid.5700447
Source: PubMed


Darier disease (DD) and Hailey-Hailey disease (HHD) are the only known autosomal-dominant Ca2+ ATPase disorders. Epidermal symptoms selectively occur in the affected individuals, the precise reason for which is still not fully understood. Here, we review the clinical, epidermal, and molecular features of the two genodermatoses. It is concluded that epidermal Ca2+ regulation disturbances and epigenetic factors may play an even more prominent role in the pathogenesis of DD and HHD than earlier appreciated.

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Available from: Richard Kellermayer, May 29, 2014
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    • "The most prominent characteristic of both HHD and DD, as discussed in numerous reviews [14] [65] [66] [67] [68], is the disruption of cell-cell contacts (acantholysis) in the suprabasal layer of the skin, which results from loss of desmosomal connections between cells. Ultrastructural studies of HHD [69] indicated that desmosomes and their connections with tonofilaments (keratin intermediate filaments) formed normally in non-lesional skin; however, in affected cells, tonofilaments separated from the desmosomes, followed by clumping of tonofilaments, loss of desmosomes, and acantholysis [69]. "
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    • "Whether the pathological phenotype of the patients depends solely on the trans-Golgi Ca 2+ reduction, on the inefficiency of Mn 2+ homeostasis and/or on the alterations of Ca 2+ /Mn 2+ handling in the secretory granules is still debated. Indirect evidence , however, suggests that modifications of Mn 2+ uptake and secretory vescicle Ca 2+ handling is not primarily involved in the disease pathogenesis, as patients affected by the Darier's disease (due to mutated SERCA2 [64], a Ca 2+ pump that does not transport Mn 2+ and is excluded from the secretory vesicles) have skin symptoms that are very similar to those of the Hailey–Hailey patients [65]. We also found that a reduction in the SPCA1 level resulted in a drastic re-organization of the overall GA morphology and a delayed traffic of proteins from the ER into the GA and eventually to the plasma membrane [29]. "
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