Nuclear envelope, nuclear lamina, and inherited disease.
The nuclear envelope is composed of the nuclear membranes, nuclear lamina, and nuclear pore complexes. In recent years, mutations in nuclear-envelope proteins have been shown to cause a surprisingly wide array of inherited diseases. While the mutant proteins are generally expressed in most or all differentiated somatic cells, many mutations cause fairly tissue-specific disorders. Perhaps the most dramatic case is that of mutations in A-type lamins, intermediate filament proteins associated with the inner nuclear membrane. Different mutations in the same lamin proteins have been shown to cause striated muscle diseases, partial lipodystrophy syndromes, a peripheral neuropathy, and disorders with features of severe premature aging. In this review, we summarize fundamental aspects of nuclear envelope structure and function, the inherited diseases caused by mutations in lamins and other nuclear envelope proteins, and possible pathogenic mechanisms.
Worman
Howard J
HJ
Department of Medicine and Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Courvalin
Jean-Claude
JC
D000818:Animals; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D034882:Lamins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009685:Nuclear Envelope / Q000378:metabolism* / Q000648:ultrastructure; D034881:Nuclear Lamina / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism
D034882:Lamins; D009687:Nuclear Proteins