MLH1 c.27G>A (p.Arg9=) 是一个同义可能/致病变体,是林奇综合征中可变的马赛克构成MLH1甲基化的基础
Rocio Alvarez1, Paula Climent-Cantó2, GiWon Shin3,4
1Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Familial cancer
|July 27, 2025
概括
以前不确定的MLH1c.27G>A变种现在被归类为可能致病的. 这是由于在林奇综合征家族中,特别是非欧洲人群中,有着马赛克MLH1表皮图的证据.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 同名MLH1变种c.27G>A (p.Arg9=) 的致病性分类不确定.
- 之前的报道缺乏实质性的临床和功能证据证明它在林奇综合征中的作用.
研究的目的:
- 重新评估MLH1c.27G>A变种的致病性.
- 调查林奇综合征中这种变异的功能机制和临床意义.
主要方法:
- 对来自欧洲和蒙古家庭的林奇综合征三例新指数病例的分析.
- 基于血液的宪法MLH1甲基化测试和分离分析.
- 对存档的瘤样本进行MLH1表达,甲基化和异性丧失的分析.
- 纳米孔测序用于变体确认和祖先分析.
主要成果:
- 三个新的MLH1c.27G>A变体家族,包括第一个非欧洲病例,显示出强烈的林奇综合征指标.
- 观察到可变的马赛克构成MLH1甲基化,与c.27A等位基因结合.
- 瘤分析显示MLH1损失,高甲基化和野生类型等位基损失,支持一种致病机制.
- 在欧洲家族中没有发现重要的共同祖先或其他候选变体.
结论:
- 现在MLH1 c.27G>A变种被归类为可能致病的.
- 一种可变的马赛克二级宪法MLH1表位的机制解释了它的致病性.
- 这一发现对林奇综合征诊断和遗传咨询有意义,特别是在多样化的群体中.
相关概念视频
02:41Lethal Alleles
15.7K
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...
15.7K
01:20Mismatch Repair
5.2K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
5.2K
02:30Histone Variants at the Centromere
4.5K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
4.5K
03:18Non-LTR Retrotransposons
11.9K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.9K