To date at least seven genes have been associated to EDMD with different inheritance patterns, being emerin gene responsible for the X-linked form of the disease.
Several murine models for EDMD have been generated; however, emerin-null (Emd) mice do not show obvious skeletal and cardiac muscle phenotypes, and Lmna H222P/H222P mutant (H222P) mice show only a mild phenotype in skeletal muscle when they already have severe cardiomyopathy.
Recent clinical research has confirmed that EDMD is one of several overlapping skeletal muscle phenotypes that can result from mutations in EMD and LMNA with dilated cardiomyopathy as a common feature.
This study enriches the EMD gene mutation database and reminds us of the possibility of EDMD while encountering patients with severe heart rhythm defects or dilated cardiomyopathy of unknown etiology, even if they have neither obvious skeletal muscle disorder nor joint involvement.
To test this, we analyzed RNA-Seq datasets, finding novel isoforms or isoform tissue-specificity for: Lap2, linked to cardiomyopathy; Nesprin 2, linked to Emery-Dreifuss muscular dystrophy and Lmo7, that regulates the Emery-Dreifuss muscular dystrophy linked emerin gene.
We have investigated Samp1 (Spindle Associated Membrane Protein 1), a transmembrane nuclear envelope protein, which interacts with emerin and lamin A, both of which are linked to Emery-Dreifuss muscular dystrophy (EDMD).
The aim of this study is to elucidate the role of emerin in rat cardiomyocytes by means of hypertrophic stimuli and in EDMD induced pluripotent stem (iPS) cell-derived cardiomyocytes in terms of nuclear structure and the Ca<sup>2+</sup> transient.
Mutations in the gene encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD), a disorder causing progressive skeletal muscle wasting, irregular heart rhythms and contractures of major tendons.
A rapamycin-based dimerization assay revealed correct transport of wild-type emerin to the INM, whereas TRC40-binding, membrane integration and INM-targeting of emerin mutant proteins that occur in EDMD was disturbed.
Mutations in the inner nuclear envelope protein emerin cause Emery-Dreifuss muscular dystrophy (EDMD), which is characterized by progressive skeletal muscle wasting, cardiac conduction defects, and tendon contractures.
Patient blood cells were predominantly emerin-positive, but considerable nuclear lobulation was observed in non-granulocyte cells - a novel phenotype in EDMD.
Our findings broaden the heterogeneous spectrum of phenotypes attributed to EMD mutations and provide new insight to explain the genotype-phenotype correlations between EMD mutations and EDMD symptoms.
These "muscle-specific" isoforms are thought to form a complex with emerin and lamin A/C at the inner nuclear membrane and mutations in all three proteins cause Emery-Dreifuss muscular dystrophy and/or inherited dilated cardiomyopathy, disorders in which only skeletal muscle and/or heart are affected.
The more common X-linked recessive form of EDMD is caused by mutations in either EMD (encoding emerin) or FHL1 (encoding four and a half LIM domains 1), while mutations in LMNA (encoding lamin A/C), SYNE1 (encoding nesprin-1) and SYNE2 (encoding nesprin-2) lead to autosomal dominant forms of the condition.
The following is a report on a large family with 5 males affected by the X-linked recessive form of Emery-Dreifuss muscular dystrophy with mutation in the STA gene.
Both Emerin and LaminA/C interact with the nuclear envelope proteins Nesprin-1 and -2 and mutations in genes encoding C-terminal isoforms of Nesprin-1 and -2 have also been implicated in EDMD.