Homozygous <i>FAT1</i> frameshift mutation linked to glomerulotubular nephropathy with impaired cell adhesion and Rap1 signaling.

ABSTRACT: Genetic mutations are closely linked to various renal diseases, revealing important molecular mechanisms that contribute to kidney dysfunction. Here, we reported a 35-year-old Chinese female diagnosed of glomerulotubular nephropathy with multiple extra-renal manifestations including ptosis, corneal dystrophy, macular degeneration, right foot syndactyly. Whole-exome sequencing identified a homozygous frameshift variant in FAT1 (NM_005245: c.7444_7445delGT, p.Val2482AsnfsTer16). Further analysis revealed that this mutation caused translation repression of FAT1. RNA sequencing showed dysregulation of cell adhesion and Rap1 signaling pathways, while immunofluorescence staining demonstrated disrupted β-catenin junctions and cytoskeletal abnormalities in patient-derived primary urinary ep

SUBMITTER: Fei Y 

PROVIDER: S-EPMC12456052 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature