• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Human mutation >An acceptor splice site mutation in the calcium-sensing receptor (CASR) gene in familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.
【24h】

An acceptor splice site mutation in the calcium-sensing receptor (CASR) gene in familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.

机译：家族性低钙血症和新生儿严重甲状旁腺功能亢进症中钙敏感受体（CASR）基因的受体剪接位点突变。

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

We studied family members of a large kindred expressing both familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT) and found, by PCR amplification of the extracellular calcium-sensing receptor (CASR) gene exons and flanking intronic sequences, that FHH individuals were heterozygous for a g to t substitution in the last nucleotide of intron 2 (IVS2-1G>T). Defects in messenger RNA splicing were investigated by illegitimate transcription of the CASR gene in lymphoblastoid cells from an FHH affected individual, as well as by transfection of a CASR minigene harboring this mutation into HEK293 cells. The mutation resulted predominantly in exon III skipping causing a shift in exon IV reading frame and introduction of a premature stop codon leading to a predicted truncated protein of 153 amino acids. Interestingly, it was noted that exon III splicing is not 100% efficient in parathyroid, thyroid, and kidney; an exon III-deleted transcript is produced approximately 15% of the time. This is the first description of a splice site mutation in the CASR gene and provides an explanation of the clinical phenotype of the patients. Copyright 2001 Wiley-Liss, Inc.
机译：我们研究了同时表达家族性低钙血症高钙血症（FHH）和新生儿严重甲状旁腺功能亢进症（NSHPT）的大家庭的成员，并通过PCR扩增细胞外钙敏感受体（CASR）基因外显子和侧翼内含子序列，发现FHH个体是内含子2的最后一个核苷酸中ag到t取代杂合（IVS2-1G> T）。通过从受FHH影响的个体的淋巴母细胞中CASR基因的非法转录，以及通过将携带该突变的CASR小基因转染到HEK293细胞中，研究了Messenger Rna剪接中的缺陷。该突变主要导致外显子III跳跃，从而导致外显子IV阅读框发生变化，并引入了提前终止密码子，导致预测的153个氨基酸的截短蛋白。有趣的是，注意到在甲状旁腺，甲状腺和肾脏中外显子III的剪接不是100％有效。大约15％的时间会产生外显子III缺失的转录本。这是对CASR基因中剪接位点突变的首次描述，并为患者的临床表型提供了解释。版权所有2001 Wiley-Liss，Inc.

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