laminopathies

’Laminopathies’ are associated with defects in proteins of the nuclear envelope. Most laminopathy mutations have been mapped to the A-type lamin gene, which is expressed in most adult cell types.

Laminopathies comprise a group of inherited diseases with variable clinical phenotypes, caused by mutations in the lamin A/C gene (LMNA).

A prominent feature in several of these diseases is muscle wasting, as seen in Emery Dreifuss muscle dystrophy, dilated cardiomyopathy and limb-girdle muscular dystrophy.

While the mechanisms underlying this phenotype remain largely obscure, two major working hypotheses are currently being investigated, namely, defects in gene regulation and/or abnormalities in nuclear architecture causing cellular fragility.

 There is a direct correlation between absence of LMNA proteins and nuclear fragility in living cells. This nuclear behaviour is indicative for a loss of interaction of the disturbed nucleus with the surrounding cytoskeleton. The tree-dimensional organisation of actin -, vimentin- and tubulin-based filaments shows a disturbed interaction of these structures in MEF-/- cells. This loss of nuclear stiffness
is associated with a loss of a physical interaction between nuclear structures (i.e. lamins) and the cytoskeleton(15367494).

Classification

 Emery-Dreifuss disease (muscle dystrophy)
 dilated cardiomyopathy
 limb-girdle muscular dystrophy

References

 Worman HJ, Bonne G. "Laminopathies": A wide spectrum of human diseases. Exp Cell Res. 2007 Mar 30; PMID: 17467691

 Broers JL, Hutchison CJ, Ramaekers FC. Laminopathies. J Pathol. 2004 Nov;204(4):478-88. PMID: 15495262

 Worman HJ, Courvalin JC. The nuclear lamina and inherited disease. Trends Cell Biol. 2002 Dec ;12(12):591-8. PMID : 12495848

 Burke B, Stewart CL. Life at the edge : the nuclear envelope and human disease. Nat Rev Mol Cell Biol. 2002 Aug ;3(8):575-85. PMID : 12154369

 Burke B, Stewart CL. Life at the edge: the nuclear envelope and human disease. Nat Rev Mol Cell Biol. 2002 Aug;3(8):575-85. 12154369