Variants in <i>WASHC3</i>, a component of the WASH complex, cause short stature, variable neurodevelopmental abnormalities, and distinctive facial dysmorphism.

ABSTRACT:

Purpose

Genetic defects that impair growth plate chondrogenesis cause a phenotype that varies from skeletal dysplasia to mild short stature with or without other syndromic features. In many individuals with impaired skeletal growth, the genetic causes remain unknown.

Method

Exome sequence was performed in 3 unrelated families with short stature, distinctive facies, and neurodevelopmental abnormalities. The impact of identified variants was studied in vitro.

Results

Exome sequencing identified variants in WASHC3, a component of the WASH complex. In the first family, a de-novo-dominant missense variant (p.L69F) impaired WASHC3 participation in the WASH complex, altered PTH1R endosomal trafficking, diminished PTH1R signaling, and affected growth plate chondrocyte

SUBMITTER: Jee YH 

PROVIDER: S-EPMC11932664 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature