扩展COL7A1突变数据库:41例营养不良性大疱表皮松解症患者中新发和再发突变及少见的基因型-表型相互影响因素  

Expanding the COL7A1 mutation database: Novel and recurrent mutations and unusual genotype-Phenotype constellations in 41 patients with dystrophic epidermolysis bullosa

作　　者：Kern J.S. Kohlhase J. Bruckner-Tuderman L. Has C 董平 

机构地区：[1]Department of Dermatology, University of Freiburg, Hauptstr.7, Freiburg 79104, Germany Dr.

出　　处：《世界核心医学期刊文摘（皮肤病学分册）》2006年第9期17-17,共1页Digest of the World Core Medical JOurnals:Dermatology

摘　　要：Dystrophic epidermolysis bullosa (DEB), a heterogeneous hereditary skin disorder characterized by trauma-induced blistering and scarring, affects thousands of families world wide. The clinical manifestations extend from minor nail dystrophy to severe life-threatening blistering, making early molecular diagnosis and prognostication of utmost importance for the affected families. DEB is caused by mutations in the COL7A1 gene encoding collagen VII in the skin. Molecular diagnostics and genotype-phenotype correlations in DEB remain complex owing to the gene structure, large variety of mutations, high rate of novel mutations, complex protein structure and assembly, and the heterogeneity of phenotypes. Here, we report an efficient strategy for COL7A1mutation detection using direct automated DNA sequencing and implementation of software tools. With this approach, COL7A1 mutations of 41 DEB families were disclosed. Twenty-four mutations were novel and two recurrent. Elucidation of biological consequences of the mutations helped define disease mechanisms, but also revealed several unusual genotypic and/or phenotypic constellations, which impeded the diagnostics and prognostication. In addition, the studies disclosed a de novo mutation in recessive DEB and two new polymorphisms in the COL7A1 gene.Dystrophic epidermolysis bullosa （DEB）, a heterogeneous hereditary skin disorder characterized by trauma-induced blistering and scarring, affects thousands of families world wide. The clinical manifestations extend from minor nail dystrophy to severe life-threatening blistering, making early molecular diagnosis and prognostication of utmost importance for the affected families. DEB is caused by mutations in the COL7A1 gene encoding collagen Ⅶ in the skin. Molecular diagnostics and genotype-phenotype correlations in DEB remain complex owing to the gene structure, large variety of mutations, high rate of novel mutations, complex protein structure and assembly, and the heterogeneity of phenotypes. Here, we report an efficient strategy for COLTAlmutation detection using direct automated DNA sequencing and implementation of software tools. With this approach, COLTA1 mutations of 41 DEB families were disclosed. Twenty-four mutations were novel and two recurrent. Elucidation of biological consequences of the mutations helped define disease mechanisms, but also revealed several unusual genotypic and/or phenotypic constellations, which impeded the diagnostics and prognostication. In addition, the studies disclosed a de novo mutation in recessive DEB and two new polymorphisms in the COLTA1 gene.

关 键 词：COL7A1突变 基因型-表型关系 大疱表皮松解症 营养不良性 影响因素 新发 再发 数据库 

分 类 号：R758.59[医药卫生—皮肤病学与性病学]