A ciliopathy combining Joubert syndrome and Oro-Facial-Digital syndrome caused by bi-allelic 5'-UTR loss-of-function CEP83 variant.

ABSTRACT: Oro-Facial-Digital Syndrome (OFDS) and Joubert syndrome are ciliary disorders. Fifteen individuals of consanguineous Bedouin kindred presented with global developmental delay with no speech, and a clear OFDS phenotype, combined with Joubert syndrome, with MRI showing hypoplastic corpus callosum and molar tooth sign. Renal and liver function tests and ultrasound were unremarkable. Within a 0.5 Mb disease-associated locus (LOD score 6.2), whole genome sequencing identified a single variant: CEP83 NG_051825.2:g.5774dupG, (NM_016122.3):c.-278dupG. Patient fibroblasts showed aberrantly long cilia, and alternative splicing of CEP83 5'UTR, skipping most of exon 1 of the canonical transcript, and frameshift, abrogating CEP83 mRNA and protein expression. CEP83 acts in primary cilium assembly. CEP83

SUBMITTER: Jean MM 

PROVIDER: S-EPMC12514222 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature