König A, Winberg J O, Gedde-Dahl T, Bruckner-Tuderman L
Department of Dermatology, University Hospital Zürich, Switzerland.
J Invest Dermatol. 1994 Feb;102(2):155-9. doi: 10.1111/1523-1747.ep12371754.
Severe mutilating recessive dystrophic epidermolysis bullosa presents with extensive blistering, scarring, and pseudosyndactylies. The skin of most affected individuals lacks normal anchoring fibrils and contains no, or drastically reduced amounts of, collagen VII, the major fibril component. Here we present evidence for molecular heterogeneity of the mutations underlying this phenotype. A patient with severe mutilating disease, but with apparently normal anchoring fibrils and abundant collagen VII, was defined. Indirect immunofluorescence examination of the patient's skin exhibited a strong staining for collagen VII at the dermo-epidermal junction and at the roof of a natural blister, and immunoblotting of skin extracts revealed collagen VII of normal size. The patient's keratinocytes expressed two- to threefold increased amounts of collagen VII at the mRNA and protein level compared to controls. Synthesis of matrix metalloproteases by the patient's keratinocytes was comparable to normal cells, indicating that the overexpression of collagen VII did not affect the synthesis of these enzymes. We hypothesize that in this patient a mutation affecting interactions of the anchoring fibrils with other components of the basement membrane zone underlies the disease.
严重致残性隐性营养不良型大疱性表皮松解症表现为广泛的水疱形成、瘢痕形成和假性并指畸形。大多数受影响个体的皮肤缺乏正常的锚定纤维，且不含或仅含有极少量的主要纤维成分VII型胶原蛋白。在此，我们提供了该表型潜在突变的分子异质性证据。确定了一名患有严重致残性疾病但锚定纤维明显正常且VII型胶原蛋白丰富的患者。对该患者皮肤进行的间接免疫荧光检查显示，在真皮-表皮交界处和天然水疱顶部，VII型胶原蛋白呈强染色，皮肤提取物的免疫印迹显示正常大小的VII型胶原蛋白。与对照组相比，该患者角质形成细胞在mRNA和蛋白质水平上表达的VII型胶原蛋白增加了两到三倍。该患者角质形成细胞中基质金属蛋白酶的合成与正常细胞相当，表明VII型胶原蛋白的过表达并未影响这些酶的合成。我们推测，在该患者中，影响锚定纤维与基底膜区其他成分相互作用的突变是该疾病的基础。
