The role of the nuclear envelope in Emery-Dreifuss muscular dystrophy.
The X-linked form of Emery-Dreifuss muscular dystrophy (X-EDMD) is caused by absence, or greatly reduced amounts, of the inner nuclear-membrane protein, emerin. The autosomal dominant form (AD-EDMD) is caused by missense mutations in lamins A and C, two components of the nuclear lamina that interact directly with emerin. Lamin A/C mutations also cause one form of dilated cardiomyopathy (CMD1A) and one form of limb-girdle muscular dystrophy (LGMD1B), both of which have clinical features in common with EDMD, as well as a rare, unrelated form of lipodystrophy (FPLD). Evidence is now emerging that defective assembly of the nuclear lamina is a feature of all these diseases, although not necessarily the direct cause. Why only heart and skeletal muscle, and possibly connective tissue, are affected in EDMD and why expression of the disease is so extremely variable between individuals remains to be explained.
Morris
G E
GE
MRIC Biochemistry Group, The North East Wales Institute, Wrexham, UK LL11 2AW. morrisge@newi.ac.uk
D000818:Animals; D005799:Genes, Dominant; D006801:Humans; D034904:Lamin Type A; D034882:Lamins; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D020125:Mutation, Missense / Q000235:genetics; D009685:Nuclear Envelope / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D013946:Thymopoietins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics
D034904:Lamin Type A; D034882:Lamins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D013946:Thymopoietins; C092710:emerin