Mutations of the α2(V) chain of type V collagen impair matrix assembly and produce Ehlers-Danlos syndrome type I
Mutations of the α2(V) chain of type V collagen impair matrix assembly and produce Ehlers-Danlos syndrome type I
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DOI：
10.1093/hmg/7.2.249
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发表时间：
1998-02-01
影响因子：
3.5
通讯作者：
Cole, WG
中科院分区：
文献类型：
--
作者：
Michalickova, K;Susic, M;Cole, WG
Ehlers-Danlos综合征（EDS）是一种异质性结缔组织疾病，严重损害皮肤、关节、眼睛和血管的结构和功能。我们已经确定了突变的COL 5A 2基因，编码α 2（V）链的V型胶原蛋白，在两个无关的患者与严重的I型EDS。第一个先证者是杂合子的7 bp缺失，导致外显子27的跳跃，而第二个先证者是杂合子的单核苷酸取代，导致外显子28的跳跃。两个先证者培养的真皮成纤维细胞产生大约等量的正常和突变的α 2（V）mRNA和蛋白质链。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变化很大。第一个先证者的骨细胞也产生大约等量的正常和突变型α 2（V）mRNA，但是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，COL 5A 2基因的杂合突变可以产生EDS I型表型，他们还表明，V型胶原在真皮胶原纤维发生中比在骨骼胶原纤维发生中发挥更重要的作用。
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 alpha 2(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 alpha 2(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 alpha 2(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.