[The laminopathy saga].
OBJECTIVE
Our aim was to clinically characterise Emery-Dreifuss muscular dystrophy, to differentiate the X-linked forms of inheritance from the forms involving autosomal dominant inheritance, from a genetic point of view, and to describe the phenotypical heterogeneity of mutations in the LMNA gene itself.


METHODS
We describe the identification of the mutations in the lamina A/C gene, the LMNA gene, which was made possible thanks to the networks allowing workers in different countries to collaborate. Mutations in this gene are responsible for autosomal dominant Emery-Dreifuss disease, as well as other diseases that are phenotypically very distinct, such as limb girdle muscular dystrophy associated with cardiac conduction defects (LGMD1B), dilated myocardiopathy with conduction defects (DCM-CD), Dunnigan-type familial partial lipodystrophy (FPLD) and, finally, an autosomal recessive form of axonal neuropathy or Charcot-Marie-Tooth disease type 2 (AR-CMT).


CONCLUSIONS
Laminas are intermediate filaments that constitute the inner nuclear membrane of any cell and the mutations in the lamina A/C gene can give rise to such distinct clinical patterns as a kind of muscular dystrophy that is similar to the well known X-linked Emery-Dreifuss disease or a form of Charcot-Marie-Tooth-type neuropathy. Work is currently being conducted on an experimental animal model capable of providing us with a better understanding of the physiopathological mechanisms involved in the production of these tissue-specific diseases, although they are due to mutations in a gene that codifies for proteins that are expressed all over.
Bonne
G
G
Inserm U523, Institut de Myologie, GH Pitié-Salpétrière, Paris, Francia.
D000818:Animals; D025063:Chromosome Disorders / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D034904:Lamin Type A / Q000235:genetics* / Q000378:metabolism; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D010641:Phenotype
D034904:Lamin Type A; C440308:lamin C