Department of Medical Science, Section of Medical Genetics, University of Ferrara, Ferrara, Italy.
BMC Med Genet. 2013 Jun 5;14:59. doi: 10.1186/1471-2350-14-59.
Mutations within the C-terminal region of the COL6A1 gene are only detected in Ullrich/Bethlem patients on extremely rare occasions.
Herein we report two Brazilian brothers with a classic Ullrich phenotype and compound heterozygous for two truncating mutations in COL6A1 gene, expected to result in the loss of the α1(VI) chain C2 subdomain. Despite the reduction in COL6A1 RNA level due to nonsense RNA decay, three truncated alpha1 (VI) chains were produced as protein variants encoded by different out-of-frame transcripts. Collagen VI matrix was severely decreased and intracellular protein retention evident.
The altered deposition of the fibronectin network highlighted abnormal interactions of the mutated collagen VI, lacking the α1(VI) C2 domain, within the extracellular matrix, focusing further studies on the possible role played by collagen VI in fibronectin deposition and organization.
COL6A1 基因 C 末端区域的突变仅在极其罕见的情况下在 Ullrich/Bethlem 患者中被检测到。
在此，我们报告了两位巴西兄弟，他们具有典型的 Ullrich 表型，COL6A1 基因存在两种截短突变的复合杂合子，预计会导致 α1(VI)链 C2 亚结构域的缺失。尽管由于无意义 RNA 降解导致 COL6A1 RNA 水平降低，但仍产生了三种截断的 α1(VI)链，这些蛋白变体由不同的移码转录本编码。胶原 VI 基质严重减少，细胞内蛋白滞留明显。
纤连蛋白网络的异常沉积突出了突变胶原 VI 的异常相互作用，突变胶原 VI 缺乏 α1(VI) C2 结构域，存在于细胞外基质中，这进一步强调了胶原 VI 在纤连蛋白沉积和组织中的可能作用。
