Genetic and functional analysis of ZMIZ1 in neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies (NEDDFSA): insights from muscle cells and signaling pathways

Our study identifies a novel likely pathogenic variant in the ZMIZ1 gene associated with NEDDFSA, the second in China, and demonstrates its functional impact on cellular processes and signaling pathways, particularly in muscle cells. This finding expands the known ZMIZ1 mutation spectrum and provides the first functional evidence of its role in muscle cells, highlighting its potential as a regulatory hub in multiple pathways beyond the nervous system. These results offer new insights into the cellular mechanisms underlying NEDDFSA, especially in non-neurological tissues, and may facilitate the development of targeted therapies for related disorders.