UNASSIGNED: We employed Whole Genome Sequencing (WGS) to explore the genetic factors in late-presenting DDH in two unrelated families, supported by phenotypic analyses and in vitro validation.
UNASSIGNED: In both cases, a novel de novo heterozygous missense mutation in RAF1 (c.193A>G [p.Lys65Glu]) was identified. This mutation impacted RAF1 protein structure and function, altering downstream signaling in the Ras/ERK pathway, as demonstrated by bioinformatics, molecular dynamics simulations, and in vitro validations.
UNASSIGNED: This study contributes to our understanding of the genetic factors involved in DDH by identifying a novel mutation in RAF1. The identification of the RAF1 mutation suggests a possible involvement of the Ras/ERK pathway in the pathogenesis of late-presenting DDH, indicating its potential role in skeletal development.
■我们使用全基因组测序(WGS)来探索两个不相关家族中DDH晚期呈递的遗传因素,由表型分析和体外验证支持。
■在这两种情况下,RAF1中的一种新的从头杂合错义突变(c.193A>G[p。Lys65Glu])被鉴定。这种突变影响了RAF1蛋白的结构和功能,改变Ras/ERK途径的下游信号,正如生物信息学所证明的那样,分子动力学模拟,和体外验证。
■这项研究通过鉴定RAF1中的一种新突变,有助于我们理解与DDH有关的遗传因素。RAF1突变的鉴定表明Ras/ERK途径可能参与晚期呈递DDH的发病机理,表明其在骨骼发育中的潜在作用。