Deciphering the pathogenic role of rare RAF1 heterozygous missense mutation in the late-presenting DDH.

ABSTRACT:

Background

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.

Methods

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.

Results

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 <

SUBMITTER: Liu Y 

PROVIDER: S-EPMC11215071 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature