A Mosaic Variant in CTNNB1/β-catenin as a Novel Cause for Osteopathia Striata With Cranial Sclerosis.

Context: Osteopathia striata with cranial sclerosis (OSCS) is a rare bone disorder with X-linked dominant inheritance, characterized by a generalized hyperostosis in the skull and long bones and typical metaphyseal striations in the long bones. So far, loss-of-function variants in AMER1 (also known as WTX or FAM123B), encoding the APC membrane recruitment protein 1 (AMER1), have been described as the only molecular cause for OSCS. AMER1 promotes the degradation of β-catenin via AXIN stabilization, acting as a negative regulator of the WNT/β-catenin signaling pathway, a central pathway in bone formation.