Prelamin A processing and functional effects in restrictive dermopathy.

Laminopathies are an heterogeneous group of human disorders caused by mutations in the lamin A/C gene or in genes coding for lamin-binding proteins. They include several tissue-specific disorders (e.g., Emery-Dreifuss muscular distrophy and dilated cardiomyopathy with conduction defects) or systemic forms including the most severe phenotypes: Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD).1 RD is a lethal neonatal laminopathy causing bone resorption of clavicles, tight translucent skin, anomalous facial features and arthrogryposis.2 RD is a secondary laminopathy, since it is associated with mutations of a lamin-binding protein, the endoprotease ZMPSTE24 involved in lamin A precursor (prelamin A) post-translational processing.3 A common mutation in the ZMPSTE24 gene (c.1085_1086InsT) has been characterized in most RD patients leading to impaired protein expression and prelamin A accumulation in cells.