PDF(Pubmed)
Abstract：
UNASSIGNED: Developmental Dysplasia of the Hip (DDH) is a skeletal disorder where late-presenting forms often escape early diagnosis, leading to limb and pain in adults. The genetic basis of DDH is not fully understood despite known genetic predispositions.
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.
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.
摘要：
■发育性髋关节发育不良（DDH）是一种骨骼疾病，晚期表现形式通常无法早期诊断，导致成人肢体和疼痛。尽管已知遗传易感性，但尚未完全了解DDH的遗传基础。
■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。
■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。
