Missense Variants in the Second Transmembrane Domain of TMEM17 Disrupt Its Stability and Function and Lead to a Wide Phenotypic Spectrum of Ciliopathies.

ABSTRACT: Ciliopathies are rare genetic disorders characterized by significant genetic and phenotypic variability. Over 140 proteins localized to primary cilia, which are sensory organelles essential for vertebrate development, are implicated. TMEM17 encodes a transmembrane protein at the ciliary transition zone and was previously proposed as a potential ciliopathy gene, based on reports of individuals from two families with orofaciodigital syndrome type 6 (OFD6) and Joubert syndrome (JS). Here, we report two unrelated fetuses with occipital encephalocele, polydactyly, and kidney cysts, in whom exome sequencing identified a founder homozygous missense variant (Arg94Trp) in TMEM17, affecting a highly conserved residue. This expands the TMEM17-associated phenotypic spectrum to include Meckel syndrome

SUBMITTER: Boutaud L 

PROVIDER: S-EPMC12779253 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature