"Laminopathies": a wide spectrum of human diseases.
Mutations in genes encoding the intermediate filament nuclear lamins and associated proteins cause a wide spectrum of diseases sometimes called "laminopathies." Diseases caused by mutations in LMNA encoding A-type lamins include autosomal dominant Emery-Dreifuss muscular dystrophy and related myopathies, Dunnigan-type familial partial lipodystrophy, Charcot-Marie-Tooth disease type 2B1 and developmental and accelerated aging disorders. Duplication in LMNB1 encoding lamin B1 causes autosomal dominant leukodystrophy and mutations in LMNB2 encoding lamin B2 are associated with acquired partial lipodystrophy. Disorders caused by mutations in genes encoding lamin-associated integral inner nuclear membrane proteins include X-linked Emery-Dreifuss muscular dystrophy, sclerosing bone dysplasias, HEM/Greenberg skeletal dysplasia and Pelger-Huet anomaly. While mutations and clinical phenotypes of "laminopathies" have been carefully described, data explaining pathogenic mechanisms are only emerging. Future investigations will likely identify new "laminopathies" and a combination of basic and clinical research will lead to a better understanding of pathophysiology and the development of therapies.
Worman
Howard J
HJ
Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA. hjw14@columbia.edu
Bonne
Gisèle
G
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D034882:Lamins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015530:Nuclear Matrix / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013577:Syndrome
D007381:Intermediate Filament Proteins; D034882:Lamins