Description

Several laminopathies are characterized by anomalous accumulation of prelamin A. Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. These proteins have an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics. Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation. Required for osteoblastogenesis and bone formation. It also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone. Mutations in lamin A produce a range of diseases that have collectively been referred to as `laminopathies’ . Two progeroid (premature aging) syndromes, Hutchinson-Gilford progeria (HGPS)and restrictive dermopathy (RD), are laminopathies that arise through defects in maturation of the lamin A precursor, prelamin A. Mandibuloacral dysplasia (MAD), which can be considered a milder form of RD, also results in accumulation of the lamin A precursor. By contrast, the majority of laminopathies are due to point mutations in the A/C lamins; these exhibit a multitude of phenotypes depending on the site of the mutation .