title: Mendelian Disorders of Cornification Caused by Defects in Intracellular Calcium Pumps: Mutation Update and Database for Variants in ATP2A2 and ATP2C1 Associated with Darier Disease and Hailey-Hailey Disease.
abstract: The two disorders of cornification associated with mutations in genes coding for intracellular calcium pumps are Darier disease (DD) and Hailey-Hailey disease (HHD). DD is caused by mutations in the ATP2A2 gene, whereas the ATP2C1 gene is associated with HHD. Both are inherited as autosomal-dominant traits. DD is mainly defined by warty papules in seborrheic and flexural areas, whereas the major symptoms of HHD are vesicles and erosions in flexural skin. Both phenotypes are highly variable. In 12%-40% of DD patients and 12%-55% of HHD patients, no mutations in ATP2A2 or ATP2C1 are found. We provide a comprehensive review of clinical variability in DD and HHD and a review of all reported mutations in ATP2A2 and ATP2C1. Having the entire spectrum of ATP2A2 and ATP2C1 variants allows us to address the question of a genotype-phenotype correlation, which has not been settled unequivocally in DD and HHD. We created a database for all mutations in ATP2A2 and ATP2C1 using the Leiden Open Variation Database (LOVD v3.0), for variants reported in the literature and future inclusions. This data may be of use as a reference tool in further research on treatment of DD and HHD.
authors.affiliation: Departments of Dermatology, Maastricht University Medical Centre, Maastricht, The Netherlands.|GROW Research School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Ruud G L
authors.initials: RG
authors.lastname: Nellen
authors.affiliation: Departments of Dermatology, Maastricht University Medical Centre, Maastricht, The Netherlands.|GROW Research School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Steijlen
authors.affiliation: Departments of Dermatology, Maastricht University Medical Centre, Maastricht, The Netherlands.|GROW Research School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.|Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Maurice A M
authors.initials: MA
authors.lastname: van Steensel
authors.affiliation: Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: Vreeburg
authors.affiliation: Departments of Dermatology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Jorge
authors.initials: J
authors.lastname: Frank
authors.affiliation: Departments of Dermatology, Maastricht University Medical Centre, Maastricht, The Netherlands.|GROW Research School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.|Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Michel
authors.initials: M
authors.lastname: van Geel
mesh_terms: D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D007644:Darier Disease / Q000235:genetics* / Q000378:metabolism; D030541:Databases, Genetic; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D009154:Mutation; D016506:Pemphigus, Benign Familial / Q000235:genetics* / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics*; D012867:Skin / Q000473:pathology
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; C403624:ATP2C1 protein, human; D000252:Calcium-Transporting ATPases; D002118:Calcium
keywords: ATP2A2; ATP2C1; Darier disease; Hailey-Hailey disease; SERCA2; SPCA1; acrokeratosis verruciformis of Hopf; genotype-phenotype correlation
  ; locus-specific database