De novo sequence variants, including truncating and splicing variants, in the additional sex‑combs like 3 gene (ASXL3) have been described as the cause of Bainbridge‑Ropers syndrome (BRS).
Bainbridge-Ropers syndrome is a genetic syndrome caused by heterozygous loss-of-function pathogenic variants in ASXL3, which encodes a protein involved in transcriptional regulation.
We identified three novel de novo heterozygous truncating variants distributed across ASXL3, outside the original cluster of ASXL3 mutations previously described for BRS.
Our findings suggest that the expression of the truncated ASXL3 protein, including ASXN and ASXH domains, give rise to BRPS, which is distinct from but overlaps with BOS.
De novo loss of function (LOF) mutations in the ASXL3 gene cause Bainbridge-Ropers syndrome, a severe form of intellectual disability (ID) and developmental delay, but there is evidence that they also occur in healthy individuals.