FBXW7 (a tumor suppressor) mutations (germline) lead to impaired ubiquitination and a neurodevelopmental syndrome
A new study published in the American Journal of Human Genetics identified monoallelic germline variants in FBXW7 (a recognized developmental regulator and tumor suppressor), within 35 individuals (from 32 families) who express global developmental delay, borderline to severe intellectual disability, hypotonia, and gastrointestinal issues. Various analyses (brain imaging, crystal-structure model of FBXW7, recombinant missense variants in cultured cells, pan-neuronal knockdown within drosophila) provide compelling evidence of an F-Box protein-related, phenotypically variable neurodevelopmental disorder associated with these variants.
- Am J Hum Genet . 2022 Apr 7;109(4):601-617