Michalickova K, Susic M, Willing M C, Wenstrup R J, Cole W G
Division of Orthopaedics, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Hum Mol Genet. 1998 Feb;7(2):249-55. doi: 10.1093/hmg/7.2.249.
Ehlers-Danlos syndrome (EDS) is a heterogeneous connective tissue disorder that severely impairs the structure and function of the skin, joints, eyes and blood vessels. We have identified mutations of the COL5A2 gene, which encodes the alpha2(V) chain of type V collagen, in two unrelated patients with the severe type I form of EDS. The first proband was heterozygous for a 7 bp deletion that resulted in skipping of exon 27 while the second proband was heterozygous for a single nucleotide substitution that resulted in skipping of exon 28. Cultured dermal fibroblasts from both probands produced about equal amounts of the normal and mutant alpha2(V) mRNAs and protein chains. The dermis from the first proband contained a sparse collagen fibrillar network with great variability in collagen fibril sizes and shapes. The dermal collagens were also abnormally soluble. Bone cells from the first proband also produced about equal amounts of the normal and mutant alpha2(V) mRNAs. However, the collagen fibrillar architecture and collagen solubility of the bone matrix were normal. Our findings show that heterozygous mutations of the COL5A2 gene can produce the EDS type I phenotype. They also suggest that type V collagen plays a more important role in collagen fibrillogenesis of dermis than that of bone.
埃勒斯-当洛综合征（EDS）是一种异质性结缔组织疾病，严重损害皮肤、关节、眼睛和血管的结构与功能。我们在两名无关的患有严重Ⅰ型EDS的患者中，鉴定出了编码Ⅴ型胶原蛋白α2（Ⅴ）链的COL5A2基因的突变。第一个先证者是7个碱基对缺失的杂合子，导致第27外显子跳跃；而第二个先证者是单个核苷酸替换的杂合子，导致第28外显子跳跃。来自这两名先证者的培养真皮成纤维细胞产生的正常和突变α2（Ⅴ）mRNA及蛋白链数量大致相等。第一个先证者的真皮含有稀疏的胶原纤维网络，胶原纤维的大小和形状差异很大。真皮中的胶原蛋白溶解性也异常。第一个先证者的骨细胞产生的正常和突变α2（Ⅴ）mRNA数量也大致相等。然而，骨基质的胶原纤维结构和胶原溶解性是正常的。我们的研究结果表明，COL5A2基因的杂合突变可产生Ⅰ型EDS表型。它们还提示，Ⅴ型胶原蛋白在真皮的胶原纤维形成中比在骨中发挥更重要的作用。
