Indexed on: 12 Apr '19Published on: 09 Apr '19Published in: EMBO Molecular Medicine
Hutchinson–Gilford progeria syndrome (HGPS) is a rare pathology caused by a specific mutation (c.1824C>T; p.G608G) in the LMNA gene (Eriksson et al, 2003). In healthy conditions, LMNA encodes lamins A and C, two major structural nuclear proteins. The mutation creates a splice site in exon 11, resulting in ubiquitous expression of progerin, an aberrant lamin A precursor. Mutations of LMNA can cause laminopathies, a group of diseases with a wide spectrum of, often overlapping, tissue-specific phenotypes. HGPS is probably one of the most devastating forms of laminopathy. Affected patients display signs of accelerated aging, such as lack of subcutaneous fat, hair loss, joint contractures, and skin thinning, and usually die prematurely from cardiovascular complications. Atherosclerosis is one of the most severe and clinically relevant features of HGPS, manifesting in the absence of classical risk factors, such as increased low-density lipoprotein and C-reactive protein (Gordon et al, 2005). In this issue, Hamczyk et al (2019) describe a mechanism for HGPS-related atherosclerosis.