相关实验视频

Updated: Jul 2, 2025

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

扩大FGFR3基因分析在骨质疏松症中扩展到非编码序列的相关性:一个案例报告

Zangbéwendé Guy Ouedraogo^1,2, Caroline Janel¹, Alexandre Janin^3,4

¹Service de Biochimie et Génétique Moléculaire, CHU Gabriel Montpied, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France.

|February 24, 2024

概括

一种新型的FGFR3内基变体导致骨发育不良,在一个成年无形发育患者中被发现. 这一发现强调了非编码变异在遗传疾病中的重要性,并有助于诊断和药物开发.

科学领域:

遗传学遗传学是一个
分子生物学分子生物学
骨生物学骨生物学

背景情况:

骨发育不良,或骨质突发发育不良,包括骨发育和生长的障碍,在许多情况下都涉及纤维细胞生长因子受体3 (FGFR3) 突变.
在FGFR3中常见的致病变体,如c.1138G>A/C和c.1620C>A/G,经常在achondroplasia和hypochondroplasia中发现.
当常见变异不存在时,诊断的挑战仍然存在,这需要精细的骨功能失调的诊断策略.

研究的目的:

在没有常见病原体变异的成年患者中调查无形质变化的遗传基础.
描述FGFR3基因中新发现的一种内基变异,并阐明其功能影响.
评估内在FGFR3变异在骨发育不良的临床相关性和诊断效用.

主要方法:

临床和放射性评估的成年患者呈现 achondroplasia 的特征.
整体外基因组测序以识别遗传变异.
在体外研究以确定已识别的内基变异的功能后果.

主要成果:

在该患者体内检测到FGFR3基因中的异质合体内基变异 (NM_000142.4:c.1075+95C>G).
试管体内分析显示,这种变异导致了异的8号内子外离子化,导致30种氨基酸在框架内插入.
这种分子机制改变了FGFR3的功能,并代表了成年人的第一个临床描述,扩大了已知的表型.

结论:

鉴定到的FGFR3内基变异是致病性的,与无色突变相关,证实了其自体主导遗传.
这种变异扩大了与FGFR3相关的骨发育不良的表型谱,并且在诊断上具有相关性.
在诊断测试中纳入内部变种检测可以提高变种检测率和患者管理,为药物开发提供信息.

关键词:

这种疾病叫做Achondroplasia.异能化异能化异能化纤维细胞生长因子受体3 过高质量细胞增生不全症是什么骨质软骨质异形质形成症.骨发育不良症骨发育不良症

更多相关视频

Laser Capture Microdissection of Mouse Embryonic Cartilage and Bone for Gene Expression Analysis

Laser Capture Microdissection of Mouse Embryonic Cartilage and Bone for Gene Expression Analysis

Published on: December 18, 2019

Author Spotlight: Three-Dimensional Cephalometric Landmark Annotation Demonstration on Human Cone Beam Computed Tomography Scans

Author Spotlight: Three-Dimensional Cephalometric Landmark Annotation Demonstration on Human Cone Beam Computed Tomography Scans

Published on: September 8, 2023

相关概念视频

Exon Recombination

Exon Recombination

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...

Incomplete Dominance

Incomplete Dominance

Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.