The first COL7A1 mutation survey in a large Spanish dystrophic epidermolysis bullosa cohort: c.6527insC disclosed as an unusually recurrent mutation

作者：Maria Jose Escamez, Marta García, Natividad Cuadrado‐Corrales, Sara Gómez Llames, A. Charlesworth, Naomi De Luca, Nuria Illera, Carolina Sanchez-Jimeno, Almudena Holguín, Blanca Duarte, M J Trujillo-Tiebas, Jose Luis Vicario, J.L. Santiago, Angela Hernández‐Martín, Antonio Torrelo, Daniele Castiglia, Carmen Ayuso, Fernando Larcher, José L. Jorcano, Álvaro Meana, Guerrino Meneguzzi, Giovanna Zambruno, Marcela Del Río · 发表于：British Journal of Dermatology · 年份：2010 · DOI：10.1111/j.1365-2133.2010.09713.x · 被引用次数：61 · 研究领域：Skin and Cellular Biology Research、Dermatological and Skeletal Disorders、Autoimmune Bullous Skin Diseases

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a genodermatosis caused by mutations in COL7A1. The clinical manifestations are highly variable from nail dystrophy to life-threatening blistering, making early molecular diagnosis and prognosis of utmost importance for the affected families. Mutation identification is mandatory for prenatal testing. OBJECTIVES: To conduct the first mutational analysis of COL7A1 in a Spanish cohort, to assess mutation consequences at protein/mRNA level and to establish genotype-phenotype correlations. METHODS: Forty-nine Spanish patients with DEB were studied. Antigen mapping was performed on patient skin biopsies. COL7A1 mutation screening in genomic DNA was performed by polymerase chain reaction (PCR) and direct sequencing. Mutation consequences were determined by reverse transcriptase-PCR. RESULTS: Eight patients belonged to three unrelated families with dominant DEB. Forty-one were affected with recessive DEB (RDEB). Specifically, 27 displayed the severe generalized subtype, eight the other generalized subtype and six a localized phenotype (two pretibial, three acral and one inversa). Thirty-five mutations were identified, 20 of which are novel. The pathogenic mutation c.6527insC accounted for 46.3% of Spanish RDEB alleles. A consistent genotype-phenotype correlation was established. CONCLUSIONS: Although the COL7A1 database indicates that most DEB mutations are family specific, the pathogenic mutation c.6527insC was highly recurrent i...