Lehmann H W, Mundlos S, Winterpacht A, Brenner R E, Zabel B, Müller P K
Institute of Medical Molecular Biology, Medical University of Lübeck, Germany.
Arch Dermatol Res. 1994;286(8):425-8. doi: 10.1007/BF00371566.
A patient suffering from a severe form of Ehlers-Danlos syndrome is presented (EDS type VII). The presence of bilateral congenital hip dislocation, generalized joint hypermobility and a soft hyperelastic skin with abnormal scarring suggested a specific collagen type I defect. SDS-PAGE analysis of collagens secreted into the medium of fibroblast cultures showed a retarded migration of more than half of the alpha 2(I) chains. CNBr peptide mapping of the HPLC-purified altered chain localized the mutant locus to the N-terminal region of the protein. cDNA analysis of the corresponding gene COL1A2 revealed, in addition to the expected collagen sequence, a transcript missing the entire exon 6. This exon encodes a major crosslinking site within collagen fibres as well as the N-propeptidase cleavage site. The skipping of exon 6 is caused by a splice site mutation substituting an A for a G at the first nucleotide of intron 6.
本文报告了一名患有严重型埃勒斯-当洛综合征（EDS VII型）的患者。双侧先天性髋关节脱位、全身关节活动过度以及伴有异常瘢痕形成的柔软且超弹性皮肤的存在提示存在特定的I型胶原缺陷。对成纤维细胞培养上清液中分泌的胶原进行SDS-PAGE分析显示，超过一半的α2（I）链迁移延迟。对HPLC纯化的改变链进行CNBr肽图谱分析，将突变位点定位到该蛋白的N端区域。对相应基因COL1A2的cDNA分析显示，除了预期的胶原序列外，还有一个缺失整个外显子6的转录本。该外显子编码胶原纤维内的一个主要交联位点以及N-前肽酶切割位点。外显子6的跳跃是由一个剪接位点突变引起的，该突变在第6内含子的第一个核苷酸处用A替代了G。
