...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American journal of medical genetics, Part A >Familial Ehlers-Danlos syndrome with lethal arterial events caused by a mutation in COL5A1
【24h】

Familial Ehlers-Danlos syndrome with lethal arterial events caused by a mutation in COL5A1

机译：由COL5A1突变引起的致死性动脉事件的家族性Ehlers-Danlos综合征

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Different forms of Ehlers-Danlos syndrome (EDS) exist, with specific phenotypes and associated genes. Vascular EDS, caused by heterozygous mutations in the COL3A1 gene, is characterized by fragile vasculature with a high risk of catastrophic vascular events at a young age. Classic EDS, caused by heterozygous mutations in the COL5A1 or COL5A2 genes, is characterized by fragile, hyperextensible skin and joint laxity. To date, vessel rupture in four unrelated classic EDS patients with a confirmed COL5A1 mutation has been reported. We describe familial occurrence of a phenotype resembling vascular EDS in a mother and her two sons, who all died at an early age from arterial ruptures. Diagnostic Sanger sequencing in the proband failed to detect aberrations in COL3A1, COL1A1, COL1A2, TGFBR1, TGFBR2, SMAD3, and ACTA2. Next, the proband's DNA was analyzed using a next-generation sequencing approach targeting 554 genes linked to vascular disease (VASCULOME project). A novel heterozygous mutation in COL5A1 was detected, resulting in an essential glycine substitution at the C-terminal end of the triple helix domain (NM_000093.4:c.4610G>T; p.Gly1537Val). This mutation was also present in DNA isolated from autopsy material of the index's brother. No material was available from the mother, but the mutation was excluded in her parents, siblings and in the father of her sons, suggesting that the COL5A1 mutation occurred in the mother's genome de novo. In conclusion, we report familial occurrence of lethal arterial events caused by a COL5A1 mutation. (c) 2015 Wiley Periodicals, Inc.
机译：存在不同形式的Ehlers-Danlos综合征（EDS），具有特定的表型和相关基因。由COL3A1基因的杂合突变引起的血管EDS的特征是脆​​弱的脉管系统，在年轻时具有发生灾难性血管事件的高风险。经典的EDS是由COL5A1或COL5A2基因的杂合突变引起的，其特征是脆弱，过度伸展的皮肤和关节松弛。迄今为止，已经报道了四例具有确认的COL5A1突变的不相关的经典EDS患者的血管破裂。我们描述了一个母亲和她的两个儿子在家族中发生的类似于血管EDS的表型，他们均在早期因动脉破裂而死亡。先证者中的Sanger诊断测序无法检测到COL3A1，COL1A1，COL1A2，TGFBR1，TGFBR2，SMAD3和ACTA2中的像差。接下来，使用针对与血管疾病相关的554个基因的下一代测序方法分析了先证者的DNA（VASCULOME项目）。在COL5A1中检测到一个新的杂合突变，导致在三螺旋结构域的C末端（NM_000093.4：c.4610G> T; p.Gly1537Val）处必需的甘氨酸取代。从该索引兄弟的尸检材料中分离出的DNA中也存在这种突变。母亲没有可用的材料，但在父母，兄弟姐妹和儿子的父亲中未发现该突变，这表明COL5A1突变发生在母亲的新基因组中。总之，我们报告了由COL5A1突变引起的致死性动脉事件的家族性发生。 （c）2015年威利期刊有限公司

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号