The functions of nuclear envelope encompass preserving the structural integrity of the nucleus, controlling molecular passage between the nucleus and cytoplasm, DNA replication and gene transcription (2, 3). Mutations in the genes encoding nuclear

envelope proteins are known to cause a wide variety of disorders, the so-called nuclear envelopathy. The number of genes related to nuclear envelopathy and their associated diseases are rapidly increasing. Among these, mutations in the emerin gene (EMD) and the lamin A/C gene (LMNA) are known to cause Emery-Dreifuss muscular dystrophy (EDMD) and limb girdle muscular dystrophy (LGMD). EDMD is clinically characterized by the triad of: early joint contractures Inhibitors,research,lifescience,medical of the elbows, Achilles tendons, and postcervical area; slowly progressive

muscle wasting and weakness with a humeroperoneal distribution in the early stages; cardiomyopathy with conduction defects that require pacemaker implantation to avoid sudden death (4). X-linked recessive (X-EDMD; OMIM 310300), autosomal dominant (AD-EDMD; Inhibitors,research,lifescience,medical OMIM 181350) and rare autosomal Inhibitors,research,lifescience,medical recessive (AR-EDMD; OMIM 604929) forms are known. In 1994, the STA (or EMD) gene was identified as the causative gene for X-EDMD (5). EMD is located on chromosome Xq28 and composed of 6 exons encoding a 254-amino acid proteinm known as emerin. Emerin is a 34-kDa integral inner nuclear membrane protein (6, 7), which is involved both in tissue-specific gene regulation and mechanical integrity of the nucleus.

At present, more than Inhibitors,research,lifescience,medical 100 mutations distributed homogeneously along the EMD gene have been reported (http://www.dmd.nl/). Most mutations create premature termination in the coding region or frame-shift mutations, and only a few missense mutations have been Inhibitors,research,lifescience,medical reported. For the screening of emerinopathy, protein analysis is quite useful. Emerin is a ubiquitously expressed nuclear membrane protein and several kinds of tissues/cells can be used for the protein analysis including biopsied skeletal and cardiac muscles, skin biopsy or fibroblasts, peripheral lymphocytes, and oral exfoliative buccal cells (6, 8–10). Almost all patients with EMD mutations show absence of emerin by immunohistochemistry the and western blotting. Only rare patients have been reported to show reduction of the protein (11). Since EMD is located on X chromosome, female find protocol carrier of the mutation can also be identified by immunohistochemistry showing mosaic expression (mixed with immunopositive and negative nuclei) of emerin. From the clinical point of view, it is important to identify the female carrier of EMD mutations because of the risk of developing lethal cardiac conduction defects (12, 13). Following the identification of EMD, mutations in LMNA were reported both in AD-EDMD and AR-EDMD (14, 15). LMNA mapped in chromosome 1q21.2-q21.