Christiano A M, Suga Y, Greenspan D S, Ogawa H, Uitto J
Department of Dermatology, Jefferson Medical College, Philadelphia, Pennsylvania 19107.
J Clin Invest. 1995 Mar;95(3):1328-34. doi: 10.1172/JCI117783.
Epidermolysis bullosa (EB) is a group of heritable mechano-bullous skin diseases classified into three major categories on the basis of the level of tissue separation within the dermal-epidermal basement membrane zone. In the most severe, dystrophic (scarring) forms of EB, blisters form below the cutaneous basement membrane at the level of the anchoring fibrils, which are composed of type VII collagen. Ultrastructural observations of altered anchoring fibrils and genetic linkage to the type VII collagen locus (COL7A1) have implicated COL7A1 as the candidate gene in the dystrophic forms of EB. We have recently cloned the entire cDNA and the gene for human COL7A1. In this study, we describe distinct mutations in both COL7A1 alleles in three brothers with severe, mutilating recessive dystrophic EB (the Hallopeau-Siemens type, HS-RDEB). The patients are compound heterozygotes for two different mutations, both of which result in a premature termination codon in COL7A1, and the parents were shown to be clinically heterozygous carries of the respective mutations. Premature termination codons in both alleles of COL7A1 appear to be the underlying cause of severe, recessive dystrophic EB in this family.
大疱性表皮松解症（EB）是一组遗传性机械性大疱性皮肤病，根据真皮 - 表皮基底膜带内组织分离的水平分为三大类。在最严重的营养不良性（瘢痕性）EB形式中，水疱在由VII型胶原蛋白组成的锚定原纤维水平的皮肤基底膜下方形成。对改变的锚定原纤维的超微结构观察以及与VII型胶原蛋白基因座（COL7A1）的遗传连锁表明COL7A1是营养不良性EB形式的候选基因。我们最近克隆了人COL7A1的完整cDNA和基因。在本研究中，我们描述了三名患有严重致残性隐性营养不良性EB（Hallopeau - Siemens型，HS - RDEB）的兄弟中COL7A1两个等位基因的不同突变。这些患者是两种不同突变的复合杂合子，这两种突变均导致COL7A1中出现过早终止密码子，并且父母被证明是各自突变的临床杂合携带者。COL7A1两个等位基因中的过早终止密码子似乎是这个家族中严重隐性营养不良性EB的根本原因。
