LMNA

About LMNA

LMNA on chromosome 1q22 encodes lamin A and lamin C, intermediate filament proteins produced by alternative splicing. Lamins form the nuclear lamina, a meshwork beneath the inner nuclear membrane that provides structural support to the nucleus, anchors chromatin, and helps regulate gene expression and mechanical signaling. LMNA variants cause a remarkably diverse group of diseases called laminopathies. Cardiac laminopathy causes dilated cardiomyopathy with conduction disease and atrial and ventricular arrhythmias, and carries a substantial risk of sudden death even when heart pumping function is only mildly reduced, so implantable devices are often considered. Other laminopathies include Emery Dreifuss muscular dystrophy, limb girdle muscular dystrophy type 1B, Dunnigan type familial partial lipodystrophy, mandibuloacral dysplasia, and Charcot Marie Tooth disease type 2B1. Hutchinson Gilford progeria syndrome, a severe premature aging disorder of childhood, is usually caused by a de novo G608G variant that activates a cryptic splice site, producing a toxic, permanently farnesylated form of lamin A called progerin. The progeria variant was identified in 2003. Small amounts of progerin also accumulate during normal aging. Lonafarnib, a farnesyltransferase inhibitor approved in 2020, extends survival in progeria.