Anderson D W, Edwards T K, Ricketts M H, Kuivaniemi H, Tromp G, Stolle C A, Deak S B, Boyd C D
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903, USA.
Ann N Y Acad Sci. 1996 Nov 18;800:216-28. doi: 10.1111/j.1749-6632.1996.tb33312.x.
Confluent skin fibroblast cultures were prepared from 40 patients diagnosed with and surgically treated for an abdominal aortic aneurysm. An analysis of secreted type I and type III collagen in the media of these fibroblast preparations revealed reduced secretion of type III collagen from six patients. DNA sequence analysis of the entire coding domain of the pro alpha 1 (III) collagen mRNA in skin fibroblast RNA from these six patients revealed a C to T substitution at nucleotide 607 in one of the probands that would result in the replacement of a leucine residue with phenylalanine in the second position of the first tripeptide repeat in the triple-helical domain of type III collagen. Allele-specific hybridization analysis of genomic DNA from this proband and family members indicated that this non-glycine substitution probably contributed to the aneurysmal phenotype in this patient. No coding sequence mutations were found in the other five patients. It is clear from this study, therefore, that aberrant synthesis of type III collagen, as a consequence of both a coding sequence mutation and other factors contributing to reduced secretion of type III procollagen, will result in the development of an aortic aneurysm in a significant percentage of patients with this disease.
从40例经诊断患有腹主动脉瘤并接受手术治疗的患者中制备了融合皮肤成纤维细胞培养物。对这些成纤维细胞培养物培养基中分泌的I型和III型胶原蛋白的分析显示，6例患者的III型胶原蛋白分泌减少。对这6例患者皮肤成纤维细胞RNA中前α1（III）型胶原蛋白mRNA的整个编码结构域进行DNA序列分析，发现其中一名先证者在核苷酸607处发生了C到T的替换，这将导致III型胶原蛋白三螺旋结构域中第一个三肽重复序列的第二个位置上的亮氨酸残基被苯丙氨酸取代。对该先证者及其家庭成员的基因组DNA进行等位基因特异性杂交分析表明，这种非甘氨酸取代可能导致了该患者的动脉瘤表型。在其他5例患者中未发现编码序列突变。因此，从这项研究中可以清楚地看出，由于编码序列突变和其他导致III型前胶原蛋白分泌减少的因素，III型胶原蛋白的异常合成将导致相当比例的这种疾病患者发生主动脉瘤。
