%0 Journal Article
%T Deciphering the pathogenic role of rare RAF1 heterozygous missense mutation in the late-presenting DDH.
%A Liu Y
%A Fan X
%A Qian K
%A Wu C
%A Zhang L
%A Yuan L
%A Man Z
%A Wu S
%A Li P
%A Wang X
%A Li W
%A Zhang Y
%A Sun S
%A Yu C
%J Front Genet
%V 15
%N 0
%D 2024
%M 38952713
%F 4.772
%R 10.3389/fgene.2024.1375736
%X <B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.