Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disorder caused 
by mutations in LMNA, which encodes the nuclear scaffold proteins lamin A and C. 
In HGPS and related progerias, processing of prelamin A is blocked at a critical 
step mediated by the zinc metalloprotease ZMPSTE24. LMNA-linked progerias can be 
grouped into two classes: (1) the processing-deficient, early onset "typical" 
progerias (e.g., HGPS), and (2) the processing-proficient "atypical" progeria 
syndromes (APS) that are later in onset. Here we describe a previously 
unrecognized progeria syndrome with prominent cutaneous and cardiovascular 
manifestations belonging to the second class. We suggest the name 
LMNA-associated cardiocutaneous progeria syndrome (LCPS) for this disorder. 
Affected patients are normal at birth but undergo progressive cutaneous changes 
in childhood and die in middle age of cardiovascular complications, including 
accelerated atherosclerosis, calcific valve disease, and cardiomyopathy. In 
addition, the proband demonstrated cancer susceptibility, a phenotype rarely 
described for LMNA-based progeria disorders. The LMNA mutation that caused LCPS 
in this family is a heterozygous c.899A>G (p.D300G) mutation predicted to alter 
the coiled-coil domain of lamin A/C. In skin fibroblasts isolated from the 
proband, the processing and levels of lamin A and C are normal. However, nuclear 
morphology is aberrant and rescued by treatment with farnesyltransferase 
inhibitors, as is also the case for HGPS and other laminopathies. Our findings 
advance knowledge of human LMNA progeria syndromes, and raise the possibility 
that typical and atypical progerias may converge upon a common mechanism to 
cause premature aging disease.