Byers P H, Duvic M, Atkinson M, Robinow M, Smith L T, Krane S M, Greally M T, Ludman M, Matalon R, Pauker S, Quanbeck D, Schwarze U
Department of Pathology, University of Washington, Seattle 98195-7470, USA.
Am J Med Genet. 1997 Oct 3;72(1):94-105. doi: 10.1002/(sici)1096-8628(19971003)72:1<94::aid-ajmg20>3.0.co;2-o.
Ehlers-Danlos syndrome (EDS) type VII results from defects in the conversion of type I procollagen to collagen as a consequence of mutations in the substrate that alter the protease cleavage site (EDS type VIIA and VIIB) or in the protease itself (EDS type VIIC). We identified seven additional families in which EDS type VII is either dominantly inherited (one family with EDS type VIIB) or due to new dominant mutations (one family with EDS type VIIA and five families with EDS type VIIB). In six families, the mutations alter the consensus splice junctions, and, in the seventh family, the exon is deleted entirely. The COL1A1 mutation produced the most severe phenotypic effects, whereas those in the COL1A2 gene, regardless of the location or effect, produced congenital hip dislocation and other joint instability that was sometimes very marked. Fractures are seen in some people with EDS type VII, consistent with alterations in mineral deposition on collagen fibrils in bony tissues. These new findings expand the array of mutations known to cause EDS type VII and provide insight into genotype/phenotype relationships in these genes.
VII型埃勒斯-当洛综合征（EDS）是由于I型前胶原转化为胶原蛋白的过程中出现缺陷所致，这是由底物中的突变引起的，这些突变改变了蛋白酶切割位点（VIIA型和VIIB型EDS）或蛋白酶本身（VII型C型EDS）。我们又发现了7个家系，其中VII型EDS要么是显性遗传（一个VIIB型EDS家系），要么是由于新的显性突变（一个VIIA型EDS家系和五个VIIB型EDS家系）。在6个家系中，突变改变了共有剪接位点，而在第7个家系中，外显子完全缺失。COL1A1突变产生了最严重的表型效应，而COL1A2基因中的突变，无论其位置或效应如何，都会导致先天性髋关节脱位和其他关节不稳定，有时这种情况非常明显。VII型EDS患者中有些人会出现骨折，这与骨组织中胶原纤维上矿物质沉积的改变一致。这些新发现扩展了已知导致VII型EDS的突变范围，并为这些基因中的基因型/表型关系提供了见解。
