• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of human genetics >Rare pseudoautosomal copy-number variations involving SHOX and/or its flanking regions in individuals with and without short stature
【24h】

Rare pseudoautosomal copy-number variations involving SHOX and/or its flanking regions in individuals with and without short stature

机译：身材矮小和没有身材矮小的个体中涉及SHOX和/或其侧翼区域的罕见假常染色体拷贝数变异

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

Pseudoautosomal region 1 (PAR1) contains SHOX, in addition to seven highly conserved non-coding DNA elements (CNEs) with cis-regulatory activity. Microdeletions involving SHOX exons 1-6a and/or the CNEs result in idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD). Here, we report six rare copy-number variations (CNVs) in PAR1 identified through copy-number analyzes of 245 ISS/LWD patients and 15 unaffected individuals. The six CNVs consisted of three microduplications encompassing SHOX and some of the CNEs, two microduplications in the SHOX 3'-region affecting one or four of the downstream CNEs, and a microdeletion involving SHOX exon 6b and its neighboring CNE. The amplified DNA fragments of two SHOX-containing duplications were detected at chromosomal regions adjacent to the original positions. The breakpoints of a SHOX-containing duplication resided within Alu repeats. A microduplication encompassing four downstream CNEs was identified in an unaffected father-daughter pair, whereas the other five CNVs were detected in ISS patients. These results suggest that microduplications involving SHOX cause ISS by disrupting the cis-regulatory machinery of this gene and that at least some of microduplications in PAR1 arise from Alu-mediated non-allelic homologous recombination. The pathogenicity of other rare PAR1-linked CNVs, such as CNE-containing microduplications and exon 6b-flanking microdeletions, merits further investigation.
机译：伪常染色体区域1（PAR1）除包含七个具有顺式调控活性的高度保守的非编码DNA元件（CNE）外，还包含SHOX。涉及SHOX外显子1-6a和/或CNE的微缺失会导致特发性矮小身材（ISS）和Leri-Weill软骨异常症（LWD）。在这里，我们报告了通过对245名ISS / LWD患者和15名未受影响的个体进行拷贝数分析而确定的PAR1中的六个罕见拷贝数变异（CNV）。六个CNV包括三个微复制，包括SHOX和一些CNE，SHOX 3'-区域中的两个微复制影响一个或四个下游CNE，以及涉及SHOX外显子6b及其相邻CNE的微缺失。在邻近原始位置的染色体区域检测到两个含有SHOX重复的扩增DNA片段。包含SHOX的重复的断点位于Alu重复中。在未受影响的父子对中鉴定出包含四个下游CNE的微复制，而在ISS患者中检测到其他五个CNV。这些结果表明，涉及SHOX的微复制会通过破坏该基因的顺式调控机制而引起ISS，并且PAR1中的至少一些微复制是由Alu介导的非等位基因同源重组产生的。其他罕见的与PAR1连锁的CNV的致病性，如含CNE的微复制和外显子6b侧翼的微缺失，值得进一步研究。

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