Emery‐Dreifuss muscular dystrophy

Abstract

Emery‐Dreifuss muscular dystrophy (EDMD) is a rare muscular dystrophy, but is particularly important to diagnose due to frequent life‐threatening cardiac complications. EDMD classically presents with muscle weakness, early contractures, cardiac conduction abnormalities and cardiomyopathy, although the presence and severity of these manifestations vary by subtype and individual. Associated genes include EMD, LMNA, SYNE1, SYNE2, FHL1, TMEM43, SUN1, SUN2, and TTN, encoding emerin, lamin A/C, nesprin‐1, nesprin‐2, FHL1, LUMA, SUN1, SUN2, and titin, respectively. The Online Mendelian Inheritance in Man database recognizes subtypes 1 through 7, which captures most but not all of the associated genes. Genetic diagnosis is essential whenever available, but traditional diagnostic tools can help steer the evaluation toward EDMD and assist with interpretation of equivocal genetic test results. Management is primarily supportive, but it is important to monitor patients closely, especially for potential cardiac complications. There is a high potential for progress in the treatment of EDMD in the coming years.

Evolution and diversification of the nuclear envelope

“…We found Alg2, Erlin2 (ER lipid raft-associated 2) and Tmem43 retained in several taxa. Mutations in Tmem43, a four transmembrane domain protein known as LUMA in Homo sapiens , are linked to cardiac conduction defects [ 97 ] and Emery-Dreifuss muscular dystrophy [ 98 , 99 ]. Moreover, Tmem43/LUMA upregulation is related to poorly fertile spermatozoa [ 100 ] and Tmem43/LUMA has close interactions with lamins and emerin and is involved in structural organization of the NE [ 99 , 101 ].…”

“…With lamina-constituting proteins being divergent in different systems [ 25 ], lamin B receptor may also constitute a case of divergence across supergroups despite its C 14 -sterol reductase domain having a pan-eukaryotic distribution and influencing metazoan cell viability and embryogenesis in plants [ 108–110 ]. Although several proteins are associated with specific diseases, such as Nesprin 1 and 2, emerin and lamin A-associated polypeptide 2 (LAP2) (Emery-Dreifuss dystrophy and cardiomyopathy) [ 98 , 111 ]; others have broad pathology, such as Sqstm1 (Sequestosome 1), associated with bone, muscle and heart defects, neurodegenerative conditions and leukemia, or EGFR (Epidermal growth factor receptor) related to cancer and bowel disease ( Table 1 ). Nesprins (Syne-1, 2 and 3) localize at the NE and are scaffolding proteins that partake in the LINC complex [ 112 , 113 ].…”

The Molecular Basis and Biologic Significance of the β-Dystroglycan-Emerin Interaction

“…In this study, we describe for the first time some molecular details underlying the interaction between β-DG and emerin and provide compelling evidence showing the biologic significance of this interplay. We focused on β-DG–emerin association because emerin is a major NE protein that modulates diverse cellular processes [ 12 , 13 ] in fact, emerin deficiency, due to mutations in its encoding gene, result in EDMD type 1, a myopathy characterized by progressive muscle degeneration and weakness and usually cardiac problems [ 22 ].…”

“…A better characterization of the interaction between of β-DG and its NE interacting partners will help to decipher the molecular basis underlying its role in critical nuclear processes. In this study, we describe in depth the interaction of β-DG with emerin, a major NE protein whose deficiency causes Emery–Dreifuss muscular dystrophy (EDMD) [ 12 , 13 ] and provide compelling evidence showing the biologic significance of their interplay.…”

Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family

“…Mutations in collagen 6α led to severe Ulrich CMD or milder Bethlem myopathy [ 24 ]. MDs showed genetic heterogeneity by sharing different clinical manifestations with the mutations in different genes, such as nine known genes associated with Emery–Dreifuss muscular dystrophy [ 30 ] and twenty-six known genes associated with limb-girdle muscular dystrophy [ 31 ]. Due to overlapping clinical symptoms and the multiple possible genetic causes for MDs and CMDs, it is difficult to obtain an accurate diagnosis for patients [ 23 , 24 ].…”