BORCS5 variants cause a spectrum of neurodevelopmental and neurodegenerative disorders with lysosomal dysfunction
A new study published in The Journal of Clinical Investigation showed biallelic variants in the BORCS5 gene, encoding a subunit of BORC complex that regulates anterograde movement and fusion of lysosomes. The variants were found among 16 individuals from 9 families, presenting with a spectrum of neurodevelopmental and neurodegenerative phenotypes based on the genotype: loss-of-function variants led to a perinatally lethal arthrogryposis multiplex congenita associated with brain malformations and diffuse prenatal neuroaxonal dystrophy, whereas missense or splice-site variants resulted in infantile-onset severe neurodegeneration with developmental epileptic encephalopathy and subsequent progressive movement disorders. Various analyses suggested an additional role of the BORCS5 gene in the modulation of lysosomal function, which could explain the distinct clinical phenotypes observed in individuals with BORCS5-related neurological disorders depending on the different impacts of BORCS5 variants on lysosomal biology.
- J Clin Invest. 2026 Apr 21;136(11):e195336