A unique missense mutation in the RING domain impairs MID1 E3 ubiquitin ligase activity and localisation and is associated with uncommon Opitz Syndrome-like signs

MID1/TRIM18 is a member of the RING-containing Tripartite Motif family of E3 ubiquitin ligases. MID1 mutations cause X-linked Opitz Syndrome (XLOS), a neurodevelopmental genetic disease. We detected a Cys56Arg substitution in a family with history of midline developmental defects as the first variant identified in MID1 catalytic RING domain. This variant affects MID1 ubiquitin E3 activity and alters MID1 subcellular localisation and microtubule dynamics in a unique manner if compared to the other XLOS-associated mutations. Our data suggest that the relationship between MID1 activity and its cellular distribution is a crucial issue to fully understand MID1 physio-pathological role.