MOLECULAR-BASIS OF THE DYSTROPHIC AND JUNCTIONAL FORMS OF EPIDERMOLYSIS-BULLOSA - MUTATIONS IN THE TYPE-VII COLLAGEN AND KALININ (LAMININ-5) GENES

被引:84
作者
UITTO, J
PULKKINEN, L
CHRISTIANO, AM
机构
[1] THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107
[2] THOMAS JEFFERSON UNIV,JEFFERSON INST MOLEC MED,MOLEC DERMATOL SECT,PHILADELPHIA,PA 19107
关键词
D O I
10.1111/1523-1747.ep12398967
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Epidermolysis bullosa (EB) is a group of heritable mechano-bullous skin diseases classified into three major categories, the simplex, junctional, and dystrophic forms, on the basis of the level of tissue separation within the dermal-epidermal basement membrane zone. Approaches of molecular biology have demonstrated that these three different forms of EB result from mutations in distinct genes: the simplex forms are due to mutations in the genes encoding keratins 5 and 14 expressed in basal keratinocytes; the junctional forms are associated with mutations in the kalinin/laminin 5 genes; and the dystrophic forms result from mutations in the type VII collagen gene (COL7A1). In this overview, we summarize our recent discoveries of pathogenic mutations in COL7A1, including premature termination codons that result in the severe, mutilating (Hallopeau-Siemens) type of recessive dystrophic EB and a glycine substitution in the collagenous region resulting in dominant dystrophic EB. Furthermore, we present evidence that implicates mutations in the kalinin/laminin 5 gamma 2 chain gene (LAMC2) in some forms of junctional EB. This information has provided the basis for DNA-based prenatal diagnosis during the first trimester of gestation, and sets the stage for the application of gene therapy to these devastating skin diseases in the future.
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收藏
页码:S39 / S46
页数:8
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