...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Medical Genetics >Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%.
【24h】

Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%.

机译：对一组Usher患者中USH1基因突变的频率进行的调查显示，钙粘着蛋白23和原粘连蛋白15基因的重要性，发现检出率超过90％。

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

BACKGROUND: Usher syndrome, a devastating recessive disorder which combines hearing loss with retinitis pigmentosa, is clinically and genetically heterogeneous. Usher syndrome type 1 (USH1) is the most severe form, characterised by profound congenital hearing loss and vestibular dysfunction. OBJECTIVE: To describe an efficient protocol which has identified the mutated gene in more than 90% of a cohort of patients currently living in France. RESULTS: The five genes currently known to cause USH1 (MYO7A, USH1C, CDH23, PCDH15, and USH1G) were tested for. Disease causing mutations were identified in 31 of the 34 families referred: 17 in MYO7A, 6 in CDH23, 6 in PCDH15, and 2 in USH1C. As mutations in genes other than myosin VIIA form nearly 50% of the total, this shows that a comprehensive approach to sequencing is required. Twenty nine of the 46 identified mutations were novel. In view of the complexity of the genes involved, and to minimise sequencing, a protocol for efficient testing of samples was developed. This includes a preliminary linkage and haplotype analysis to indicate which genes to target. It proved very useful and demonstrated consanguinity in several unsuspected cases. In contrast to CDH23 and PCDH15, where most of the changes are truncating mutations, myosin VIIA has both nonsense and missense mutations. Methods for deciding whether a missense mutation is pathogenic are discussed. CONCLUSIONS: Diagnostic testing for USH1 is feasible with a high rate of detection and can be made more efficient by selecting a candidate gene by preliminary linkage and haplotype analysis.
机译：背景：Usher综合征是一种毁灭性的隐性疾病，将听力损失与色素性视网膜炎相结合，在临床和遗传上都是异质的。 1型Usher综合征（USH1）是最严重的形式，其特征是先天性严重听力下降和前庭功能障碍。目的：描述一种有效的方案，该方案已在目前居住在法国的90％以上的患者队列中鉴定出突变基因。结果：测试了目前已知导致USH1的五个基因（MYO7A，USH1C，CDH23，PCDH15和USH1G）。在涉及的34个家庭中，有31个发现了引起疾病的突变：MYO7A中为17，CDH23中为6，PCDH15中为6，USH1C中为2。由于肌球蛋白VIIA以外的基因突变占总数的近50％，因此表明需要一种全面的测序方法。在46个已识别的突变中，有29个是新颖的。考虑到所涉及基因的复杂性，并为了最大程度地减少测序，开发了一种有效测试样品的方案。这包括初步的连锁和单倍型分析，以指示要靶向的基因。它被证明是非常有用的，并且在一些未曾预料的情况下证明了血缘关系。与CDH23和PCDH15的大多数变化都是截断突变相反，肌球蛋白VIIA既有无义突变也有错义突变。讨论了确定错义突变是否是致病性的方法。结论：USH1的诊断测试是可行的，具有较高的检出率，并且可以通过初步连锁和单倍型分析选择候选基因来提高诊断效率。

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