Expanding the clinical and molecular spectrum of TBC1D32-related ciliopathy: case reports and literature Review

Abstract

Genetic defects in primary cilia-related genes are associated with a heterogeneous group of disorders known as ciliopathies. TBC1D32-related ciliopathy presents with a broad phenotypic spectrum, ranging from isolated retinal diseases to severe multisystemic involvement, including fetal demise. We report two unrelated patients with retinal disease and hypopituitarism, with one also exhibiting facial dysmorphism, developmental delay, and unilateral oculomotor nerve palsy. Whole genome sequencing identified biallelic TBC1D32 variants in both patients, including two splice-site variants. RNA analysis revealed exon skipping, leading to frameshift and premature protein truncation. A review of previously reported cases highlighted facial dysmorphism, retinal disease, and hypopituitarism as major clinical features of TBC1D32-related ciliopathy. Additionally, we propose oculomotor nerve palsy as an extended clinical feature of this disorder. This study expands the clinical and molecular spectrum of TBC1D32-related ciliopathy.