title: Genotype-phenotype correlation in italian patients with dystrophic epidermolysis bullosa.
abstract: Dystrophic epidermolysis bullosa (DEB) is a rare skin disorder that is clinically heterogeneous and is transmitted either in dominant (DDEB) or recessive (RDEB) mode. Nevertheless, all variants of DEB are caused by mutations in type VII collagen gene (COL7A1). We report an analysis of COL7A1 mutations in 51 Italian DEB patients, 27 affected with Hallopeau-Siemens RDEB, 19 with non Hallopeau-Siemens RDEB, two with DDEB, two with pretibial RDEB, and one with inversa RDEB. Forty-one mutations were identified, 18 of which are novel. Mutation consequences were analyzed at the mRNA and protein level and genotype-phenotype correlation was determined. Recessive inheritance of a new case of pretibial RDEB was also established. In RDEB patients, six recurrent mutations were identified: 7344G-->A, 425A-->G, 8441-14del21, 4783-1G-->A, 497insA, and G1664A, the last three being found only in Italian patients. Indeed, haplotype analysis supported propagation of ancestral mutated alleles within the Italian population for these particular mutations. Altogether recurrent mutations account for approximately 43% of RDEB alleles in Italian patients and therefore new DEB patients should first be screened for the presence of these mutations.
authors.affiliation: Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology, Medical Faculty, University of Brescia, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Gardella
authors.forename: Daniele
authors.initials: D
authors.lastname: Castiglia
authors.forename: Patrizia
authors.initials: P
authors.lastname: Posteraro
authors.forename: Silvia
authors.initials: S
authors.lastname: Bernardini
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Zoppi
authors.forename: Mauro
authors.initials: M
authors.lastname: Paradisi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tadini
authors.forename: Sergio
authors.initials: S
authors.lastname: Barlati
authors.forename: John A
authors.initials: JA
authors.lastname: McGrath
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
authors.forename: Marina
authors.initials: M
authors.lastname: Colombi
mesh_terms: D024143:Collagen Type VII / Q000235:genetics; D004252:DNA Mutational Analysis; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics* / Q000473:pathology*; D005838:Genotype; D006801:Humans; D007558:Italy; D020125:Mutation, Missense; D010641:Phenotype; D012867:Skin / Q000473:pathology*
chemical_list: D024143:Collagen Type VII