LAMINOPATHIES

Laminopathies are a diverse group of genetic disorders arising from mutations in LMNA gene encoding A-type lamins A & C, filament proteins of nuclear lamina/membrane of most somatic cells. The first-described laminopathies were diseases of striated muscle such as autosomal-dominant Emery-Dreifuss muscular dystrophy (EDMD). The life-threatening feature of EDMD is dilated cardiomyopathy with early conduction system abnormalities. LMNA mutations have also been associated with cases of congenital muscular dystrophy (CMD) with heart involvement. Some other diseases related to LMNA mutation are Limb-girdle muscular dystrophy, Heart-hand syndrome, Dunnigan-type familial partial lipodystrophy, Mandibuloacral dysplasia, Hutchinson-Gilford progeria syndrome.
Dr. Worman’s (Chair, AlloMek SAB) group in 2007 discovered that activities of MAP kinases are abnormally increased in hearts of mice with an Lmna mutation corresponding to one that causes cardiomyopathy and muscular dystrophy in human subjects. Series of experiments following this discovery in his group showed that inhibition MAP kinase(especially MEK kinase 1/2) signaling in this mouse model ameliorates skeletal and cardiac muscle pathology.