Disease relevance of Muscular Dystrophy, Emery-Dreifuss

• By analogy with the human X-chromosome, we conclude that the region in the mouse around the G6pd and St14-1 loci may contain two genes corresponding to distinct human myopathies: Emery Dreifuss muscular dystrophy which is known to be closely linked to St14-1 in man and the DMD homologue described here [1].
• Mutations in the lamin A/C gene (LMNA) cause a variety of human diseases including Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy, and Hutchinson-Gilford progeria syndrome [2].
• Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked humeroperoneal dystrophy associated with cardiomyopathy that is distinct from the Duchenne and Becker forms of X-linked muscular dystrophy [3].
• Molecular evidence that the p55 gene is not responsible for either of two Xq28-linked disorders: Emery-Dreifuss muscular dystrophy and dyskeratosis congenita [4].
• Recent evidence has revealed that mutations in A-type lamins give rise to a range of rare, but dominant, genetic disorders, including Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy with conduction-system disease and Dunnigan-type familial partial lipodystrophy [5].

High impact information on Muscular Dystrophy, Emery-Dreifuss

• Mutations in the STA gene at the Xq28 locus have been found in patients with X-linked Emery-Dreifuss muscular dystrophy (EDMD) [6].
• These include the mislocalization of emerin, an inner nuclear membrane protein, defects in which are implicated in Emery-Dreifuss muscular dystrophy (EDMD), one of the three major X-linked dystrophies [7].
• These findings show that LEM domain proteins are essential for cell division and that Ce-emerin and Ce-MAN1 share at least one and possibly multiple overlapping functions, which may be relevant to Emery-Dreifuss muscular dystrophy [8].
• Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy [9].
• This gene had previously been shown to be altered in autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD-AD) and in dilated cardiomyopathy and conduction-system disease [10].

Chemical compound and disease context of Muscular Dystrophy, Emery-Dreifuss

• Besides the typical findings for Emery-Dreifuss muscular dystrophy, both patients showed an unusual early onset of cardiac symptoms at age 6 and 9 years, respectively, coinciding with unusual high creatine kinase [11].

Biological context of Muscular Dystrophy, Emery-Dreifuss

• We chose the LMNA H222P 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 [12].
• Recently, the FPLD gene was mapped to chromosome 1q21-22, which harbours the LMNA gene encoding nuclear lamins A and C. Mutations in LMNA were shown to underlie autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD-AD), which is characterized by regional and progressive skeletal muscle wasting and cardiac effects [13].
• SSCP detection of novel mutations in patients with Emery-Dreifuss muscular dystrophy: definition of a small C-terminal region required for emerin function [14].
• The cell cycle dependent mislocalisation of emerin may contribute to the Emery-Dreifuss muscular dystrophy phenotype [15].
• Early onset of X-linked Emery-Dreifuss muscular dystrophy in a boy with emerin gene deletion [16].

Anatomical context of Muscular Dystrophy, Emery-Dreifuss

• Genetic studies have now shown that people with mutations in either lamins A/C or emerin, a nuclear membrane protein, develop Emery-Dreifuss muscular dystrophy [17].
• Expression of a mutant lamin A that causes Emery-Dreifuss muscular dystrophy inhibits in vitro differentiation of C2C12 myoblasts [18].
• Expression and subcellular distribution of emerin were studied in lymphoblastoid cell lines established from four patients with Emery-Dreifuss muscular dystrophy containing different mutations in the emerin gene [19].

Gene context of Muscular Dystrophy, Emery-Dreifuss

• Mutations in emerin cause X-linked recessive Emery-Dreifuss muscular dystrophy [8].
• LAP2 isoforms have been found to share a homologous approximately 40 amino acid long region, the LEM domain, with nuclear membrane proteins MAN1 and emerin, which has been implicated in Emery-Dreifuss muscular dystrophy [20].
• These results suggest that Btf localization is regulated by apoptotic signals, and that loss of emerin binding to Btf may be relevant to muscle wasting in Emery-Dreifuss muscular dystrophy [21].
• Phenotypically, they present as Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscle dystrophy 1B (LGMD1B), or dilated cardiomyopathy with conduction defects (DCM-CD) [22].
• The product of the X-linked Emery-Dreifuss muscular dystrophy gene is a protein called emerin, which is localized to the nuclear membrane [19].

Analytical, diagnostic and therapeutic context of Muscular Dystrophy, Emery-Dreifuss

• Confocal immunofluorescence microscopy studies of the intracellular targeting of truncated forms of emerin, some of which are found in patients with Emery-Dreifuss muscular dystrophy, show that the nucleoplasmic, amino-terminal domain is necessary and sufficient for nuclear retention [23].

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