Systematic correlation of phenotype with genotype is a key goal of the emerging field of phenomics, which is expected to help define complex diseases. Careful evaluation of phenotype-genotype associations in monogenic disorders, such as
laminopathies, might provide new hypotheses to be tested with molecular and cellular studies and might also suggest potential new intervention strategies. For instance, evaluation of the clinical features of carriers of mutant LMNA in kindreds with
familial partial lipodystrophy suggests rational, staged intervention using established
pharmaceutical agents to prevent cardiovascular complications not just for patients with
lipodystrophy but by extension for patients with the common
metabolic syndrome. Careful non-invasive imaging shows phenotypic differences between partial
lipodystrophy due to mutant LMNA and not due to mutant LMNA. Furthermore, hierarchical cluster analysis detects systematic relationships between organ involvement in
laminopathies and mutation position in the LMNA genomic sequence. However, sometimes the same LMNA mutation can underlie markedly different clinical phenotypes; cellular and molecular experiments can help to explain the mechanistic basis for such differences. Finally, promising novel treatment modalities for
laminopathies, such as farnesyl
transferase inhibition and gene-based
therapies, might help not only to illuminate mechanisms that link genotype to phenotype, but also to provide hope for patients suffering with
laminopathies, since these treatments are designed to modulate key early or proximal steps in the pathogenesis of these disorders.