Deciphering the pathogenic role of rare RAF1 heterozygous missense mutation in the late-presenting DDH.
Front Genet
; 15: 1375736, 2024.
Article
em En
| MEDLINE
| ID: mdl-38952713
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 in vitro validations.Conclusion:
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.
Texto completo:
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Base de dados:
MEDLINE
Idioma:
En
Revista:
Front Genet
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China