Ser194Leu DSG2突变,与心律失常的左心室心肌病变和心室心力衰竭相关
Miry Blich1, Yaniv Zohar2, Victoria Cohen-Kaplan3
1Cardiology Division, Rambam Health Care Campus, Haifa, Israel.
Pacing and clinical electrophysiology : PACE
|February 20, 2024
概括
德斯莫格林2 (DSG2) Ser194Leu突变是心律失常性心肌病变 (AC) 的致病原因. 这种遗传变异导致细胞变化,包括中断的间隔盘,导致心室心律不整.
科学领域:
- 心血管遗传学 心血管遗传学
- 分子心脏病学分子心脏病学
- 遗传性心肌病是一种遗传性心肌病.
背景情况:
- 节律失常性心肌病 (AC) 涉及心肌的纤维脂肪替代,导致危险的心律失常.
- 德斯莫格林2 (DSG2) 基因的遗传变异与AC有关,但准确的分类对于患者的护理至关重要.
- 区分致病性DSG2变异与良性变异对于有效的治疗和家庭查至关重要.
研究的目的:
- 在被诊断为AC的患者中调查DSG2 Ser194Leu变异的致病性.
- 阐明这种特定的DSG2突变影响的细胞和分子机制.
主要方法:
- 整体外基因组测序确定了DSG2 Ser194Leu变异在心室动脉冲动症的AC患者中.
- 电子显微镜和免疫组织化学染色在内肌心活检样本上进行.
主要成果:
- 电子显微镜揭示了受影响心肌细胞中的扩大粘附结和无组织的间隙盘.
- 免疫组织化学显示,在试验物体中,desmoglein 2 (DSG2) 和connexin 43 (CX43) 的表达减少.
- 在试验者的心脏组织中观察到减少DSG2和CX43表达和周核积累.
结论:
- DSG2 Ser194Leu变异被归类为一种致病性误解突变.
- 这种突变与心律失常的左心室心肌病变有关.
- 这些发现突显了DSG2突变在AC病变发生过程中的结构和分子后果.
更多相关视频
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
33.8K
07:15Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
11.0K
相关概念视频
01:28Mechanism of Cardiac Arrhythmias
920
Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
920
02:41Lethal Alleles
15.4K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
15.4K
02:18Alternative RNA Splicing
21.2K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.2K
01:43Sex-linked Disorders
102.1K
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
102.1K