线粒体复合体I核子单元中的衰退变异是被低估的光学缩的原因
Claudio Fiorini1, Neringa Jurkute2,3,4, Alessandra Torraco5
1IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, 40139 Bologna, Italy.
Brain : a journal of neurology
|November 14, 2025
概括
复杂I (CI) 核基因的遗传查揭示了遗传性视神经病变 (ION) 的新原因. 这项研究强调了CI基因变异在视力缩和自体逆性勒伯遗传视力神经病变 (arLHON) 中的重要作用.
科学领域:
- 遗传学和分子生物学
- 神经科学是一个神经科学.
- 眼科医生 眼科 眼科
背景情况:
- 遗传性视神经病变 (ION) 具有复杂的遗传基础,涉及核和线粒体基因组.
- 编码线粒体复合体I (CI) 子单元的核基因中的致病变体在一些ION病例中涉及.
- 了解光缩的遗传原因的全谱对于诊断和治疗至关重要.
研究的目的:
- 用下一代测序 (NGS) 识别光学缩患者核复合I (CI) 基因中的致病性遗传变异.
- 描述与已识别的CI基因变异相关的临床表型.
- 评估特定的CI子单元和组合因子在不同形式的视觉神经病变中所扮演的角色,包括自身遗传性Leber遗传性视觉神经病变 (arLHON).
主要方法:
- 在31名来自23个视力缩家族的患者中进行了复杂I (CI) 基因的NGS查.
- 进行了全面的临床评估,包括神经成像 (MRI) 和神经评估.
- 利用分子结构建模来评估已识别的变种的病原性.
主要成果:
- 在31名患者中的11个核CI相关基因中确定了双或半变异.
- 观察到核心CI子单元的缺陷主要导致孤立的光学缩,而辅助子单元和组装因子的缺陷导致了一系列的表型.
- 相关的新型基因 (NDUFS7,NDUFV1,NDUFAF2,NDUFAF4,NDUFAF8) 与 12 个患有亚急性视力丧失的病例中的自体递归的利伯遗传性视力神经病变 (arLHON) 现型.
结论:
- 核复合I (CI) 基因在遗传性视神经病变 (ION) 的发病过程中起着至关重要的作用.
- 自体递归的勒伯遗传光神经病变 (arLHON) 现型与众多核CI基因有关,其中一些变体导致了arLHON和光缩.
- 常规ION基因查应包括所有CI相关基因,因为它们的流行率显著且可能被低估.
更多相关视频
06:53Visualization of Mitochondrial Respiratory Function using Cytochrome C Oxidase / Succinate Dehydrogenase COX/SDH Double-labeling Histochemistry
Published on: November 23, 2011
37.6K
08:45Determination of Mitochondrial Respiration and Glycolysis in Ex Vivo Retinal Tissue Samples
Published on: August 4, 2021
4.8K
相关概念视频
ATP Synthase: Mechanism
16.6K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
16.6K
Genetic Lingo
113.6K
Overview
113.6K
Photoreceptors and Visual Pathways
8.7K
At the molecular level, visual signals trigger transformations in photopigment molecules, resulting in changes in the photoreceptor cell's membrane potential. The photon's energy level is denoted by its wavelength, with each specific wavelength of visible light associated with a distinct color. The spectral range of visible light, classified as electromagnetic radiation, spans from 380 to 720 nm. Electromagnetic radiation wavelengths exceeding 720 nm fall under the infrared category,...
8.7K
Animal Mitochondrial Genetics
8.9K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
8.9K
The Retinoblastoma Gene
4.6K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.6K
Mitochondrial Precursor Proteins
3.5K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
Most of the mitochondrial...
3.5K
