We used the heart-selective alpha-myosin heavy chain promoter to drive expression in transgenic mice of human wild-type and M371Klamin A, which causes EDMD.
We hypothesized that the analogy between the regional muscle wasting in EDMD-AD and the regional adipocyte degeneration in FPLD, in addition to its chromosomal localization, made LMNA a good candidate gene for FPLD.
We chose the LMNAH222P missense mutation identified in a family with autosomal dominant Emery-Dreifuss muscular dystrophy, one of the striated muscle-specific laminopathies, to create a faithful mouse model of this type of laminopathy.
Twenty-three different mutations of LMNA have so far been shown to cause autosomal-dominant Emery-Dreifuss muscular dystrophy (EDMD2), three mutations were reported to cause limb-girdle muscular dystrophy (LGMD1B), eight mutations are known to result in dilated cardiomyopathy (CMD1A), and seven mutations were reported to cause familial partial lipodystrophy (FPL).
To identify disease-specific transcripts for EDMD, we applied a leave-one-out (LOO) cross-validation approach using LMNA patient muscle as a test data set, with reverse transcription-polymerase chain reaction (RT-PCR) validations in both LMNA and emerin patient muscle.
They are caused by mutations in collagen VI (ColVI) genes (COL6A1, COL6A2, and COL6A3) while LMNA mutations cause autosomal dominant Emery-Dreifuss muscular dystrophy.
They are caused by mutations in collagen VI (ColVI) genes (COL6A1, COL6A2, and COL6A3) while LMNA mutations cause autosomal dominant Emery-Dreifuss muscular dystrophy.
These results suggest that lamin A/C-mediated NMJ defects contribute to the AD-EDMD disease phenotype and provide insights into the cellular and molecular mechanisms for the muscle-specific phenotype of AD-EDMD.
These include lamin A/C in autosomal dominant Emery-Dreifuss muscular dystrophy, SMN in spinal muscular atrophy, SIX5 in myotonic dystrophy, calpain3 in type 2A limb-girdle muscular dystrophy, PABP2 in oculopharyngeal dystrophy, androgen receptor in spinal and bulbar muscular atrophy and the ataxins in hereditary ataxias.
The R249Q mutation is located within the central rod domain of the LMNA gene, and has been described in at least five unrelated sporadic EDMD2 patients.
The R249Q mutation is located within the central rod domain of the LMNA gene, and has been described in at least five unrelated sporadic EDMD2 patients.
The finding of site-specific amino acid substitutions in limb-girdle muscular dystrophy type 1B, autosomal dominant Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy type 1A, autosomal dominant partial lipodystrophy, and, now, AR-CMT2 suggests the existence of distinct functional domains in lamin A/C that are essential for the maintenance and integrity of different cell lineages.
The aim of this study was to evaluate the spectrum of muscle involvement on MRI in patients with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2) due to mutations in the lamin A/C gene and to compare it to the pattern found in other conditions with similar phenotype.
Point mutations that cause dilated cardiomyopathy (L85R and N195K) and autosomal dominant Emery-Dreifuss muscular dystrophy (L530P) modify the assembly properties of lamins A and C and cause partial mislocalization of emerin, an inner nuclear membrane protein, in HeLa cells.
Our studies in myoblasts from Emery-Dreifuss muscular dystrophy 2, a <i>LMNA</i>-linked disease affecting skeletal and cardiac muscles, demonstrated that Ankrd2 is a lamin A-binding protein and that mutated lamins found in Emery-Dreifuss muscular dystrophy change the dynamics of Ankrd2 nuclear import, thus affecting oxidative stress response.