A Novel BORCS5 Loss-Of-Function Variant in a Patient With a Rare Neurodevelopmental Disorder.
Arif Mahmood, Abid Ali Shah, Gohar Zaman et al.
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From the abstract
The BORCS5 is an important and critical component of the BLOC-one-related complex (BORC), involved in kinesin-dependent anterograde lysosomal transport. Aberrations in the octameric protein complex encompass lethal neurological manifestations, such as arthrogryposis multiplex congenita, brain malformations and neuropathological evidence of diffuse neuroaxonal dystrophy.
Reported results
Genetic analysis identified a novel stop-gain variant (NM_058169.6, c.262C>T; NP_477517.1, p.(Gln88*)) in BORCS5, subsequently confirmed by Sanger sequencing. The variant is likely pathogenic (PVS1, PM2, PP3). Protein modelling of the BORCS5; p.(Gln88*) variant showed a distinct conformation compared with the wild-type BORCS5, suggesting a potential role for the unfolded protein response in the pathogenesis of…
Authors' conclusions
In summary, our findings exemplify a novel stop-gain variant in BORCS5 associated with diverse pathological manifestations, underscoring the importance of further exploring this gene in patients lacking identifiable disease-causing gene variants.