在SREBF1中,一种功能增益变异会导致与先天性白内障相关的全身性皮肤色素增多
Huijun Wang1, Yuan Wu2, Jennifer A Bassetti3
1Dermatology Hospital, Southern Medical University, Guangzhou, China.
The British journal of dermatology
|July 15, 2024
概括
斯特罗尔调节元素结合蛋白1 (SREBP-1) 的新型遗传变异导致皮肤多颜色和先天性白内障的新疾病. 这项研究突出了SREBP-1的重点.
科学领域:
- 遗传学和分子生物学
- 皮肤病学 皮肤病学
- 眼科医生 眼科 眼科
背景情况:
- 脂质新陈代谢对于皮肤屏障功能,炎症和黑色素形成至关重要.
- 固醇调节元素结合蛋白1 (SREBP-1) 是细胞脂质代谢的关键调节者.
- SREBF1变种与皮肤角质化障碍有关.
研究的目的:
- 确定一种新型疾病的遗传原因,该疾病表现为扩散性皮肤多色素和先天性白内障.
- 阐明SREBF1变异对疾病发病有所贡献的机制.
主要方法:
- 整体外基因组测序以识别遗传变异.
- 定量PCR,西斑和免疫光分析SREBP-1表达和定位.
- 路西法酶记者测定以评估转录活动.
- 开发一个转基因斑马鱼模型.
主要成果:
- 确定了两名患有全身性皮肤色素增多,光化,先天性白内障和皮肤外症状的患者.
- 在这两名患者中都发现了SREBF1中的一个新的无意义变体 (c.1289C>A,p.Ser430*).
- 突变的SREBP-1显示出偏好的核定位和增强的转录活性,导致黑色素细胞中的黑色素合成增加.
- 转基因斑马鱼呈现出增加的色素和升调的黑色素基因.
结论:
- 在SREBF1中,一种功能增益变异会导致以前未被识别的疾病,其特征是全身性皮肤色素增多和先天性白内障.
- SREBP-1 在黑色素发生和透镜发育中起着重要作用.
- 这项研究确定了皮肤色素变化和白内障的潜在治疗点.
更多相关视频
12:37Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
18.2K
06:39Differentiation, Maintenance, and Analysis of Human Retinal Pigment Epithelium Cells: A Disease-in-a-dish Model for BEST1 Mutations
Published on: August 24, 2018
6.7K
相关概念视频
01:33Pleiotropy
40.4K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.4K
01:20The Retinoblastoma Gene
4.1K
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,...
4.1K
01:11Genetic Lingo
102.6K
Overview
102.6K
01:39Epistasis
46.6K
In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...
46.6K
02:27Background and Environment Affect Phenotype
6.5K
Although the genetic makeup of an organism plays a major role in determining the phenotype, there are also several environmental factors, such as temperature, oxygen availability, presence of mutagens, that can alter an organism’s phenotype.
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
6.5K
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