The nuclear lamina contributes to the regulation of gene expression and to 
chromatin organization. Mutations in A-type nuclear lamins cause laminopathies, 
some of which are associated with a loss of heterochromatin at the nuclear 
periphery. Until recently however, little if any information has been provided 
on where and how lamin A interacts with the genome and on how disease-causing 
lamin A mutations may rearrange genome conformation. Here, we review aspects of 
nuclear lamin association with the genome. We highlight recent evidence of 
reorganization of lamin A-chromatin interactions in cellular models of 
laminopathies, and implications on the 3-dimensional rearrangement of chromatin 
in these models, including patient cells. We discuss how a hot-spot 
lipodystrophic lamin A mutation alters chromatin conformation and epigenetic 
patterns at an anti-adipogenic locus, and conclude with remarks on links between 
lamin A, Polycomb and the pathophysiology of laminopathies. The recent findings 
presented here collectively argue towards a deregulation of large-scale and 
local spatial genome organization by a subset of lamin A mutations causing 
laminopathies.