WDTC1 Haploinsufficiency as a Cause of Neurodevelopmental Phenotypes

WDTC1 haploinsufficiency, cullin-RING E3 ubiquitin ligase complex subunit, dysregulation of lipid storage and proteasome

7 individuals carrying heterozygous loss-of-function variants in WDTC1 are described with a neurodevelopmental syndrome featuring intellectual disability, seizures, and dysmorphic features. WDTC1 encodes a component of cullin-RING E3 ubiquitin ligase complexes involved in proteasomal degradation and lipid storage regulation. The cohort includes 6 newly reported cases (some de novo) and confirms a variable phenotypic spectrum with behavioral abnormalities and inconsistent obesity. This publication establishes WDTC1 as a new autosomal dominant NDD gene.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

WDTC1 enriches the group of NDD genes linked to the ubiquitin-proteasome pathway (UPS). The NDD + variable obesity association points to a specific diagnostic target and recalls other UPS genes (UBE3A, NEDD4L). A potential therapeutic axis via the mTOR/lipid pathway warrants literature monitoring.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 2/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 8/10