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Alterations of nuclear envelope and chromatin organization in mandibuloacral dysplasia, a rare form of laminopathy.

Authors: Filesi, Ilaria  Gullotta, Francesca  Lattanzi, Giovanna  D'Apice, Maria Rosaria  Capanni, Cristina  Nardone, Anna Maria  Columbaro, Marta  Scarano, Gioacchino  Mattioli, Elisabetta  Sabatelli, Patrizia  Maraldi, Nadir M  Biocca, Silvia  Novelli, Giuseppe 
Citation: Filesi I, etal., Physiol Genomics. 2005 Oct 17;23(2):150-8. Epub 2005 Jul 26.
Pubmed: (View Article at PubMed) PMID:16046620
DOI: Full-text: DOI:10.1152/physiolgenomics.00060.2005

Autosomal recessive mandibuloacral dysplasia [mandibuloacral dysplasia type A (MADA); Online Mendelian Inheritance in Man (OMIM) no. 248370] is caused by a mutation in LMNA encoding lamin A/C. Here we show that this mutation causes accumulation of the lamin A precursor protein, a marked alteration of the nuclear architecture and, hence, chromatin disorganization. Heterochromatin domains are altered or completely lost in MADA nuclei, consistent with the finding that heterochromatin-associated protein HP1beta and histone H3 methylated at lysine 9 and their nuclear envelope partner protein lamin B receptor (LBR) are delocalized and solubilized. Both accumulation of lamin A precursor and chromatin defects become more severe in older patients. These results strongly suggest that altered chromatin remodeling is a key event in the cascade of epigenetic events causing MADA and could be related to the premature-aging phenotype.


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CRRD Object Information
CRRD ID: 12791023
Created: 2017-02-28
Species: All species
Last Modified: 2017-02-28
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.