Smith L T, Wertelecki W, Milstone L M, Petty E M, Seashore M R, Braverman I M, Jenkins T G, Byers P H
Department of Biological Structure, University of Washington, Seattle 98195.
Am J Hum Genet. 1992 Aug;51(2):235-44.
Dermatosparaxis is a recessively inherited connective-tissue disorder that results from lack of the activity of type I procollagen N-proteinase, the enzyme that removes the amino-terminal propeptides from type I procollagen. Initially identified in cattle more than 20 years ago, the disorder was subsequently characterized in sheep, cats, and dogs. Affected animals have fragile skin, lax joints, and often die prematurely because of sepsis following avulsion of portions of skin. We recently identified two children with soft, lax, and fragile skin, which, when examined by transmission electron microscopy, contained the twisted, ribbon-like collagen fibrils characteristic of dermatosparaxis. Skin extracts from one child contained collagen precursors with amino-terminal extensions. Cultured fibroblasts from both children failed to cleave the amino-terminal propeptides from the pro alpha 1(I) and pro alpha 2(I) chains in type I procollagen molecules. Extracts of normal cells cleaved to collagen, the type I procollagen synthesized by cells from both children, demonstrating that the enzyme, not the substrate, was defective. These findings distinguish dermatosparaxis from Ehlers-Danlos syndrome type VII, which results from substrate mutations that prevent proteolytic processing of type I procollagen molecules.
皮肤松弛症是一种隐性遗传的结缔组织疾病，由I型前胶原N蛋白酶缺乏活性所致，该酶负责从I型前胶原中去除氨基末端前肽。20多年前在牛身上首次发现这种疾病，随后在绵羊、猫和狗身上也有相关特征描述。患病动物皮肤脆弱、关节松弛，常因皮肤部分撕裂后继发败血症而过早死亡。我们最近发现了两名儿童，他们的皮肤柔软、松弛且脆弱，经透射电子显微镜检查，其皮肤含有皮肤松弛症特有的扭曲、带状胶原纤维。其中一名儿童的皮肤提取物含有带有氨基末端延伸的胶原前体。两名儿童的培养成纤维细胞均无法从I型前胶原分子的α1（I）前体链和α2（I）前体链上切割氨基末端前肽。正常细胞提取物能将两名儿童细胞合成的I型前胶原切割成胶原，这表明是酶有缺陷，而非底物有缺陷。这些发现将皮肤松弛症与VII型埃勒斯-当洛综合征区分开来，后者是由底物突变导致I型前胶原分子无法进行蛋白水解加工引起的。
