Am J Hum Genet 2022 04;109(4):601-617
The Genomic Unit, Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel; The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel.
Neurodevelopmental disorders are highly heterogenous conditions resulting from abnormalities of brain architecture and/or function. FBXW7 (F-box and WD-repeat-domain-containing 7), a recognized developmental regulator and tumor suppressor, has been shown to regulate cell-cycle progression and cell growth and survival by targeting substrates including CYCLIN E1/2 and NOTCH for degradation via the ubiquitin proteasome system. We used a genotype-first approach and global data-sharing platforms to identify 35 individuals harboring de novo and inherited FBXW7 germline monoallelic chromosomal deletions and nonsense, frameshift, splice-site, and missense variants associated with a neurodevelopmental syndrome. Read More