Calcium pump disorders of the skin.
The causes of Darier disease (DD) and Hailey-Hailey disease (HHD) have eluded clinicians and scientists for more than 60 years. DD is characterized by loss of adhesion between suprabasal epidermal cells associated with abnormal keratinization, while loss of epidermal cell-to-cell adhesion is predominant in HHD. The genes for both conditions have recently been identified using candidate positional cloning approaches. The gene for DD (ATP2A2) encodes a calcium transport ATPase of the sarco (endo)plasmic reticulum (SERCA2) Verboomen et al. [1992: Biochem J 286(Pt 2):591-595], while the gene for HHD (ATP2C1) codes for a secretory pathway for calcium and manganese transport ATPase of the Golgi apparatus (SPCA1) Hu et al. [2000: Nat Genet 24:61-65]. These results have provided completely new insights into the role of calcium and/or manganese in maintaining skin integrity. Although the precise disease mechanisms remain to be understood, these discoveries open a new field in research for the understanding and the treatment of these distressing disorders.
Department of Medical Genetics, Pavillon Lefebvre, Purpan Hospital, Place du Dr Baylac, Toulouse cedex 03, France.
Lucie
L
Foggia
Alain
A
Hovnanian
D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics*; D007644:Darier Disease / Q000235:genetics*; D003937:Diagnosis, Differential; D006056:Golgi Apparatus / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D016506:Pemphigus, Benign Familial / Q000235:genetics*; D017434:Protein Structure, Tertiary; D012519:Sarcoplasmic Reticulum / Q000235:genetics; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; C403624:ATP2C1 protein, human; D000252:Calcium-Transporting ATPases; D002118:Calcium