HRAS变异c.175G>A (p.Ala59Thr) 导致一种主要是外皮的表型,缺乏古典科斯特罗综合征的特征
Nikole Rautiainen1, Eveliina Brandt1, Kaisa Kettunen2
1Department of Dermatology and Allergology, ERN-Skin Center, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
American journal of medical genetics. Part A
|October 11, 2025
概括
一种新的HRAS基因变异,c.175G>A (p.Ala59Thr),导致一种较轻的Costello综合征 (CS),具有外皮特征. 这一发现有助于诊断具有类似症状的RASopathies.
科学领域:
- 遗传学 是一个遗传学.
- 皮肤病学 皮肤病学
- 罕见疾病 罕见疾病
背景情况:
- 科斯特罗综合征 (CS) 是一种罕见的主导RAS病变,由HRAS基因突变引起.
- 在58-60编码子中的特定HRAS变异与较温和的临床表现有关.
- 外皮异常是某些RAS病态表型的关键特征.
研究的目的:
- 在一个三代家族中描述一种新型异质合体HRAS变体 (c.175G>A,p.Ala59Thr).
- 为了研究与这种特定HRAS变异相关的临床表型.
- 为了区分这种表型与经典的科斯特洛综合征.
主要方法:
- 使用外体和桑格测序进行遗传分析.
- 临床评估,包括皮肤和心脏评估.
- 皮肤活检和头发样本的显微镜检查.
主要成果:
- 在受影响的家庭成员中确定了以前未报告的HRAS变异c.175G>A (p.Ala59Thr).
- 观察到一个一致的表型,主要涉及外皮特征:羊毛/稀疏的头发,卷曲的眼,稀疏的眉毛,ulerythema ophryogenes,皮质炎,棕植物皮质炎和耳朵异常.
- 经典的科斯特洛综合征特征,如面异常,多变性心肌病和智力障碍显著缺席或最小.
结论:
- HRAS c.175G>A (p.Ala59Thr) 变异导致一种主要的外皮表型,代表了HRAS相关RASopathy的较温和形式.
- 这种表型与经典的科斯特罗综合征有区别,特别是由于缺乏严重的系统性参与.
- 对于准确的诊断和管理,考虑在表皮外和科斯特罗综合征样特征的患者中考虑HRAS变异至关重要.
相关概念视频
01:11Genetic Lingo
113.8K
Overview
113.8K
02:38The Ras Gene
7.0K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
7.0K
02:18Alternative RNA Splicing
24.7K
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...
24.7K
01:33Pleiotropy
43.2K
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,...
43.2K
01:49Multiple Allele Traits
37.9K
The Concept of Multiple Allelism
37.9K
02:41Lethal Alleles
17.7K
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...
17.7K