相关实验视频

Updated: Jan 7, 2026

In Vivo Modeling of the Morbid Human Genome using Danio rerio

In Vivo Modeling of the Morbid Human Genome using Danio rerio

Published on: August 24, 2013

通过精心策划的基因型-表型存储库,改善库伦-德弗里斯综合征的变异解释和诊断

Hailin Huang¹, Jia Geng¹, Yang Long²

¹Department of Otolaryngology-Head & Neck Surgery, Institute of Rare Diseases, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Molecular genetics and genomics : MGG

|December 28, 2025

概括

库伦-德弗里斯综合征 (KdVS) 是一种复杂的神经发育障碍. 这项研究创建了一个基因型-表型存储库,通过分析相互关联的临床特征和KANSL1变异来改进遗传诊断.

科学领域:

遗传学是一个遗传学.
神经科学是一个神经科学.
罕见疾病罕见疾病

背景情况:

神经发育障碍 (NDD) 由于复杂的基因型-表型相关性而存在诊断挑战,导致诊断产量低 (~40%).
库伦 - 德弗里斯综合征 (KdVS),由KANSL1哈普洛缺陷引起,是一种自体主导的NDD,具有多样化的表现和不明确的基因型-表型关系.
目前对NDD的诊断方法经常产生不确定的变体解释.

研究的目的:

通过整合全球文献数据,为KdVS建立一个全面的基因型-表型存储库.
系统地分析KdVS中的基因型-表型关联,以了解其相互关联的临床特征.
通过特定疾病的存储库方法,提高KdVS和其他罕见NDD的遗传诊断.

主要方法:

从全球文献中系统地整合分子确诊的KdVS病例.
综合的表型分析,以确定核心特征和特征之间的相关性.
该存储库的应用用于选中国罕见病队列并对KANSL1变异进行分类.

主要成果:

确定了KdVS的核心特征:发育迟缓/智力障碍,面形,低血压和多系统异常.
发现了249个显著的基因型-表型相关性,突出了KdVS表现的相互联系性质 (例如,偏头症和水头症,OR=14.26).
在一个中国患者中确定了一种致病性KANSL1变异,并对52种意义不明的变异 (VUS) 进行分类,以促进表型驱动的重新解释.

结论:

KdVS是一种高度相互连接的多系统障碍.
深度表型关联分析显著提高了NDDs的遗传诊断.
一个特定于疾病的存储库框架为改善罕见NDD的分子诊断提供了一个可扩展的解决方案.

关键词:

中国队列的中国队列.基因型表型库基因型表型库在KANSL1的KANSL1上.库伦·德弗里斯综合征 (KdVS) 是一种不确定意义的变体 (VUS)

更多相关视频

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

相关概念视频

Incomplete Dominance

Incomplete Dominance

Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.

Pleiotropy

Pleiotropy

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,...

Karyotyping

Karyotyping

Pedigree Analysis

Pedigree Analysis

Genome-wide Association Studies-GWAS

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...

Genomics

Genomics

Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...