title: Molecular characterization of 11 Italian patients with Darier disease.
abstract: Darier disease (DD) is an autosomal dominant genodermatosis characterized by multiple warty papules coalescing in seborrheic areas and specific histological skin changes. Heterozygous mutations in ATP2A2, encoding the sarco-endoplasmic reticulum calcium pumping ATPase type 2, are identified as the molecular basis of DD. In this study, molecular features in a large cohort of Italian patients are reported. Molecular data were collected along with the main clinical features. Genomic DNA was used for direct sequencing of ATP2A2. The effect of selected mutations was predicted by in silico analysis or investigated by gene expression studies. 10 different ATP2A2 mutations were identified. Three mutations (c.2300A>G, c.2794G>A, c.569delAins34) have been previously described, while 7, including 2 missense (c.545G>A and c.2116G>A), 2 nonsense (c.1372G>T and c.1675C>T), 1 small deletion (c.142delA), 1 duplication (c.2935_2949dup15) and 1 splice-site mutation (c.2742-1G>A), were novel. Collected data added new variants to the ATP2A2 repertoire and confirmed that ATP2A2 mutations are scattered over the entire gene and, in most cases, private.
authors.affiliation: Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy. lucia.pedace@email.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Pedace
authors.forename: Luana
authors.initials: L
authors.lastname: Barboni
authors.forename: Erika
authors.initials: E
authors.lastname: Pozzetto
authors.forename: Ada
authors.initials: A
authors.lastname: Amantea
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Preziosi
authors.forename: Francesco
authors.initials: F
authors.lastname: Benedicenti
authors.forename: Stefania
authors.initials: S
authors.lastname: Boni
authors.forename: Davide
authors.initials: D
authors.lastname: De Brasi
authors.forename: Chiara
authors.initials: C
authors.lastname: Panetta
authors.forename: Carmela
authors.initials: C
authors.lastname: Ferraro
authors.forename: Carmelilia
authors.initials: C
authors.lastname: De Bernardo
authors.forename: Marco
authors.initials: M
authors.lastname: Castori
authors.forename: Paola
authors.initials: P
authors.lastname: Grammatico
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D007644:Darier Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D009154:Mutation; D010375:Pedigree; D015995:Prevalence; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D004247:DNA; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human