RNA-First方法识别了X链接的低酸性风病中的深度内部PHEX变体
Karissa Ludwig1, Zenghui Wu1, Ghalib Bardai1
1Shriners Hospital for Children - Canada, Montreal, QC, Canada.
The Journal of clinical endocrinology and metabolism
|November 8, 2024
概括
在常规检测失败时,PHEX基因的深层内基因变异会导致X结合性低血性狂犬病 (XLH) 的错误拼接. 这项研究在XLH患者中发现了新的PHEX拼接缺陷,改善了诊断产量.
科学领域:
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
- 儿科内分泌学 儿科内分泌学
背景情况:
- 与X结合的低血性狂风病 (XLH) 是一种影响和代谢的遗传疾病.
- 常规基因检测未能在高达20%的XLH患者中识别致病变体.
- 确定新的遗传原因对于准确诊断和管理XLH至关重要.
研究的目的:
- 调查PHEX基因内的内基变异,导致XLH患者的错误拼接.
- 提高标准分子检测不具结论的XLH病例的诊断率.
主要方法:
- 在临床XLH诊断的四名儿科患者中分析PHEX基因的RNA和DNA序列.
- 培养尿源细胞,提取mRNA,进行cDNA合成和PCR放大.
- 测序PHEXcDNA和内部DNA区域以确定拼接异常和致病变体.
主要成果:
- 在四分之三的参与者中检测到PHEX错误拼接.
- 在PHEX中鉴定出新型内变异:内13 (删除),内17 (激活密码拼接供体位) 和内21 (导致伪外的包含).
- 这些变异导致了外因子跳转或伪外因子结合,破坏了正常的PHEX基因功能.
结论:
- 与PHEX内测序相结合的RNA分析可以识别常规外聚焦遗传检测中遗漏的深层内变异.
- 这种方法可以提高XLH的分子诊断在患有未解释的表型的患者.
- 这些发现扩大了已知的PHEX突变导致XLH的谱.
关键词:
菲克斯 (PHEX) 是一个词.骨组织形态测量 骨组织形态测量在Exon跳过的情况下,Exon跳过.伪外星人 伪外星人Rickets Rickets 拉基茨 拉基茨是一个疾病.与X相关的低酸血症.更多相关视频
09:37Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
9.7K
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
33.6K
相关概念视频
02:32Exon Recombination
3.6K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...
Exon shuffling follows “splice frame rules.” Each exon...
3.6K
01:31Translation
141.6K
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
141.6K