Disclosed herein are point mutations in the LMNA
gene that cause HGPS. These mutations activate a cryptic splice site within the LMNA
gene, which leads to deletion of part of
exon 11 and generation of a
mutant Lamin A
protein product that is 50 amino acids shorter than the
normal protein. In addition to the novel Lamin A variant
protein and nucleic acids encoding this variant, methods of using these molecules in detecting biological conditions associated with a LMNA
mutation in a subject (e.g., HGPS,
arteriosclerosis, and other age-related diseases), methods of treating such conditions, methods of selecting treatments, methods of screening for compounds that influence Lamin A activity, and methods of influencing the expression of LMNA or LMNA variants are also described. Oligonucleotides and other compounds for use in examples of the described methods are also provided, as are
protein-specific binding agents, such as antibodies, that bind specifically to at least one
epitope of a Lamin A variant protein preferentially compared to wildtype Lamin A, and methods of using such antibodies in diagnosis, treatment, and screening. Also provided are kits for carrying out the methods described herein.