Biallelic variants in FAT3 cause axonal neuropathy with multisystem neurodevelopmental features - PubMed
5 hours ago
- #neurodevelopmental disorder
- #axonal neuropathy
- #FAT3
- Biallelic variants in FAT3 are implicated in inherited axonal neuropathies, affecting three unrelated Japanese patients among 3,315 with inherited peripheral neuropathies.
- Patients exhibited progressive distal muscle weakness, cranial nerve involvement (e.g., tongue atrophy, dysarthria), and two required ventilatory support due to respiratory muscle paralysis.
- One patient showed additional features, including central hypomyelination, autonomic dysfunction, and developmental anomalies like congenital scoliosis and intestinal pseudo-obstruction.
- Identified FAT3 variants are ultra-rare, affect conserved residues, segregate with disease, and are predicted to impair domain stability.
- Functional studies in Drosophila and mouse models confirm FAT3's role, with knockdowns causing motor defects, shortened lifespan, and motor neuron branching issues, and knockouts leading to axonal degeneration and CNS abnormalities.
- FAT3 is established as a novel gene for autosomal recessive axonal neuropathies, linked to a multisystem neurodevelopmental disorder with motor neuron degeneration and systemic abnormalities.