emery dreifuss muscular dystrophy

Summary

Summary: A heterogenous group of inherited muscular dystrophy without the involvement of nervous system. The disease is characterized by MUSCULAR ATROPHY; MUSCLE WEAKNESS; CONTRACTURE of the elbows; ACHILLES TENDON; and posterior cervical muscles; with or without cardiac features. There are several INHERITANCE PATTERNS including X-linked (X CHROMOSOME), autosomal dominant, and autosomal recessive gene mutations.

Top Publications

  1. Rowinska Marcinska K, Szmidt Sałkowska E, Fidzianska A, Zalewska E, Dorobek M, Karwanska A, et al. Atypical motor unit potentials in Emery-Dreifuss muscular dystrophy (EDMD). Clin Neurophysiol. 2005;116:2520-7 pubmed
    ..Our special interest was focused on high amplitude polyphasic motor unit potentials (MUPs), also termed irregular MUPs...
  2. Nagano A, Koga R, Ogawa M, Kurano Y, Kawada J, Okada R, et al. Emerin deficiency at the nuclear membrane in patients with Emery-Dreifuss muscular dystrophy. Nat Genet. 1996;12:254-9 pubmed
    ..A 34 kD protein is immunoreactive with the antisera--the protein is equivalent to that predicted for emerin. Together, our findings suggest the specific deficiency of emerin in the nuclear membrane of muscle cells in patients with EDMD...
  3. Tsukahara T, Tsujino S, Arahata K. CDNA microarray analysis of gene expression in fibroblasts of patients with X-linked Emery-Dreifuss muscular dystrophy. Muscle Nerve. 2002;25:898-901 pubmed
    ..Our preliminary results suggest a correlation between disease similarity and gene expression. We conclude that the cDNA microarray is a very efficient tool to clarify genetic and pathological features of diseases...
  4. Arimura T, Helbling Leclerc A, Massart C, Varnous S, Niel F, Lacene E, et al. Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies. Hum Mol Genet. 2005;14:155-69 pubmed
    ..These results demonstrate that LmnaH222P/H222P mice represent a good model for studying laminopathies affecting striated muscles as they develop a dystrophic condition of both skeletal and cardiac muscles similar to the human diseases...
  5. Clements L, Manilal S, Love D, Morris G. Direct interaction between emerin and lamin A. Biochem Biophys Res Commun. 2000;267:709-14 pubmed
    ..An emerin-lamin A interaction system may be related in function to the LAP2-lamin B system at the inner nuclear rim...
  6. Zhang Q, Bethmann C, Worth N, Davies J, Wasner C, Feuer A, et al. Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Hum Mol Genet. 2007;16:2816-33 pubmed
    ..Taken together, these data suggest that EDMD may be caused, in part, by uncoupling of the nucleoskeleton and cytoskeleton because of perturbed nesprin/emerin/lamin interactions...
  7. Cartegni L, Di Barletta M, Barresi R, Squarzoni S, Sabatelli P, Maraldi N, et al. Heart-specific localization of emerin: new insights into Emery-Dreifuss muscular dystrophy. Hum Mol Genet. 1997;6:2257-64 pubmed
    ..In heart its specific localization to desmosomes and fasciae adherentes could account for the characteristic conduction defects described in patients...
  8. Muchir A, Pavlidis P, Bonne G, Hayashi Y, Worman H. Activation of MAPK in hearts of EMD null mice: similarities between mouse models of X-linked and autosomal dominant Emery Dreifuss muscular dystrophy. Hum Mol Genet. 2007;16:1884-95 pubmed
    ..Activation of MAPK signaling appears to be a cornerstone in the development of heart disease in both X-linked and autosomal dominant EDMD...
  9. Muchir A, Pavlidis P, Decostre V, Herron A, Arimura T, Bonne G, et al. Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy. J Clin Invest. 2007;117:1282-93 pubmed
    ..Activation of MAPK signaling by mutant A-type lamins could be a cornerstone in the development of heart disease in autosomal dominant Emery-Dreifuss muscular dystrophy...

More Information

Publications62

  1. Capell B, Collins F. Human laminopathies: nuclei gone genetically awry. Nat Rev Genet. 2006;7:940-52 pubmed
  2. Mittelbronn M, Hanisch F, Gleichmann M, Stötter M, Korinthenberg R, Wehnert M, et al. Myofiber degeneration in autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD) (LGMD1B). Brain Pathol. 2006;16:266-72 pubmed
    ..Methods included quantitative light and electron microscopy and PCR-based mutational analysis...
  3. Bakay M, Wang Z, Melcon G, Schiltz L, Xuan J, Zhao P, et al. Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb-MyoD pathways in muscle regeneration. Brain. 2006;129:996-1013 pubmed
    ..Our data is consistent with mutations of nuclear lamina components leading to destabilization of the transcriptome in differentiated cells...
  4. Haraguchi T, Holaska J, Yamane M, Koujin T, Hashiguchi N, Mori C, et al. Emerin binding to Btf, a death-promoting transcriptional repressor, is disrupted by a missense mutation that causes Emery-Dreifuss muscular dystrophy. Eur J Biochem. 2004;271:1035-45 pubmed
    ..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...
  5. Holt I, Ostlund C, Stewart C, Man N, Worman H, Morris G. Effect of pathogenic mis-sense mutations in lamin A on its interaction with emerin in vivo. J Cell Sci. 2003;116:3027-35 pubmed
    ..Subtle effects on the function of the lamina-emerin complex in EDMD/CMD1A patients might be responsible for the skeletal and/or cardiac muscle phenotype...
  6. Liu J, Lee K, Segura Totten M, Neufeld E, Wilson K, Gruenbaum Y. MAN1 and emerin have overlapping function(s) essential for chromosome segregation and cell division in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2003;100:4598-603 pubmed
    ..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...
  7. Favreau C, Dubosclard E, Ostlund C, Vigouroux C, Capeau J, Wehnert M, et al. Expression of lamin A mutated in the carboxyl-terminal tail generates an aberrant nuclear phenotype similar to that observed in cells from patients with Dunnigan-type partial lipodystrophy and Emery-Dreifuss muscular dystrophy. Exp Cell Res. 2003;282:14-23 pubmed
    ..Transfected cells therefore develop similar phenotypes when expressing lamins mutated in the carboxyl-terminal tail at sites responsible for FPLD or EDMD...
  8. Talkop U, Talvik I, Sõnajalg M, Sibul H, Kolk A, Piirsoo A, et al. Early onset of cardiomyopathy in two brothers with X-linked Emery-Dreifuss muscular dystrophy. Neuromuscul Disord. 2002;12:878-81 pubmed
    ..The two boys described here belong to the very few Emery-Dreifuss muscular dystrophy patients with early onset of cardiac involvement and contribute to the variability of cardiac symptoms in Emery-Dreifuss muscular dystrophy...
  9. Wilkinson F, Holaska J, Zhang Z, Sharma A, Manilal S, Holt I, et al. Emerin interacts in vitro with the splicing-associated factor, YT521-B. Eur J Biochem. 2003;270:2459-66 pubmed
    ..YT521-B joins a growing list of candidates for a role in a gene expression model of the pathogenesis of EDMD...
  10. Bonne G, Di Barletta M, Varnous S, Becane H, Hammouda E, Merlini L, et al. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. Nat Genet. 1999;21:285-8 pubmed
    ..Together with mutations in EMD (refs 5,6), they underscore the potential importance of the nuclear envelope components in the pathogenesis of neuromuscular disorders...
  11. Raharjo W, Enarson P, Sullivan T, Stewart C, Burke B. Nuclear envelope defects associated with LMNA mutations cause dilated cardiomyopathy and Emery-Dreifuss muscular dystrophy. J Cell Sci. 2001;114:4447-57 pubmed
    ..Taken together, these results suggest that nuclear structural defects could contribute to the etiology of both dilated cardiomyopathy and autosomal dominant Emery-Dreifuss muscular dystrophy...
  12. Raffaele di Barletta M, Ricci E, Galluzzi G, Tonali P, Mora M, Morandi L, et al. Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy. Am J Hum Genet. 2000;66:1407-12 pubmed
  13. Ellis J. Emery-Dreifuss muscular dystrophy at the nuclear envelope: 10 years on. Cell Mol Life Sci. 2006;63:2702-9 pubmed
  14. Motsch I, Kaluarachchi M, Emerson L, Brown C, Brown S, Dabauvalle M, et al. Lamins A and C are differentially dysfunctional in autosomal dominant Emery-Dreifuss muscular dystrophy. Eur J Cell Biol. 2005;84:765-81 pubmed
  15. Broers J, Kuijpers H, Ostlund C, Worman H, Endert J, Ramaekers F. Both lamin A and lamin C mutations cause lamina instability as well as loss of internal nuclear lamin organization. Exp Cell Res. 2005;304:582-92 pubmed
    ..Our findings suggest a loss of function of A-type lamin mutant proteins in the organization of intranuclear chromatin and predict the loss of gene regulatory function in laminopathies...
  16. Sabatelli P, Lattanzi G, Ognibene A, Columbaro M, Capanni C, Merlini L, et al. Nuclear alterations in autosomal-dominant Emery-Dreifuss muscular dystrophy. Muscle Nerve. 2001;24:826-9 pubmed
  17. Bengtsson L, Wilson K. Multiple and surprising new functions for emerin, a nuclear membrane protein. Curr Opin Cell Biol. 2004;16:73-9 pubmed
    ..These interactors imply multiple roles for emerin in the nucleus, some of which overlap with related LEM-domain proteins...
  18. Vaughan A, Alvarez Reyes M, Bridger J, Broers J, Ramaekers F, Wehnert M, et al. Both emerin and lamin C depend on lamin A for localization at the nuclear envelope. J Cell Sci. 2001;114:2577-90 pubmed
    ..Elimination of these lamins from the lamina led to the accumulation of emerin as aggregates within the ER. Our data suggest that lamin A is essential for anchorage of emerin to the inner nuclear membrane and of lamin C to the lamina...
  19. Bione S, Maestrini E, Rivella S, Mancini M, Regis S, Romeo G, et al. Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy. Nat Genet. 1994;8:323-7 pubmed
  20. Fidzianska A, Hausmanowa Petrusewicz I. Architectural abnormalities in muscle nuclei. Ultrastructural differences between X-linked and autosomal dominant forms of EDMD. J Neurol Sci. 2003;210:47-51 pubmed
    ..The muscle biopsies were taken from rectus femoris in four X-linked EDMD cases and three ADEDMD cases...
  21. Morris G. The role of the nuclear envelope in Emery-Dreifuss muscular dystrophy. Trends Mol Med. 2001;7:572-7 pubmed
    ..Why only heart and skeletal muscle, and possibly connective tissue, are affected in EDMD and why expression of the disease is so extremely variable between individuals remains to be explained...
  22. Ki C, Hong J, Jeong G, Ahn K, Choi K, Kim D, et al. Identification of lamin A/C ( LMNA) gene mutations in Korean patients with autosomal dominant Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy 1B. J Hum Genet. 2002;47:225-8 pubmed
    ..To our knowledge, this is the first report of LMNA gene mutations in Korean patients with EDMD2 and LGMD1B...
  23. Puckelwartz M, Kessler E, Zhang Y, Hodzic D, Randles K, Morris G, et al. Disruption of nesprin-1 produces an Emery Dreifuss muscular dystrophy-like phenotype in mice. Hum Mol Genet. 2009;18:607-20 pubmed publisher
    ..membrane proteins lamins A and C produce cardiac and skeletal muscle dysfunction referred to as Emery Dreifuss muscular dystrophy. Lamins A and C participate in the LINC complex that, along with the nesprin and SUN proteins, LInk ..
  24. Muchir A, Worman H. Emery-Dreifuss muscular dystrophy. Curr Neurol Neurosci Rep. 2007;7:78-83 pubmed
  25. Fatkin D, MacRae C, Sasaki T, Wolff M, Porcu M, Frenneaux M, et al. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. N Engl J Med. 1999;341:1715-24 pubmed
    ..Mutations in the head or tail domain of this gene cause Emery-Dreifuss muscular dystrophy, a childhood-onset disease characterized by joint contractures and in some cases by abnormalities of cardiac conduction during adulthood...
  26. Fairley E, Riddell A, Ellis J, Kendrick Jones J. The cell cycle dependent mislocalisation of emerin may contribute to the Emery-Dreifuss muscular dystrophy phenotype. J Cell Sci. 2002;115:341-54 pubmed
    ..These results suggest that emerin links A-type lamins to the nuclear envelope and that the correct localisation of these nuclear proteins is important for maintaining cell cycle timing...
  27. Worman H, Bonne G. "Laminopathies": a wide spectrum of human diseases. Exp Cell Res. 2007;313:2121-33 pubmed
    ..Future investigations will likely identify new "laminopathies" and a combination of basic and clinical research will lead to a better understanding of pathophysiology and the development of therapies...
  28. Wilson K. The nuclear envelope, muscular dystrophy and gene expression. Trends Cell Biol. 2000;10:125-9 pubmed
    ..This article discusses these and other recent results in the wider context of nuclear envelope function, as a framework for thinking about the possible ways in which defects in nuclear envelope proteins can lead to disease...
  29. Melcon G, Kozlov S, Cutler D, Sullivan T, Hernandez L, Zhao P, et al. Loss of emerin at the nuclear envelope disrupts the Rb1/E2F and MyoD pathways during muscle regeneration. Hum Mol Genet. 2006;15:637-51 pubmed
    ..We suggest that the dominant LMNA mutations seen in many clinically disparate laminopathies may similarly alter Rb function, with regard to either the timing of exit from the cell cycle or terminal differentiation programs or both...
  30. Mejat A, Decostre V, Li J, Renou L, Kesari A, Hantai D, et al. Lamin A/C-mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy. J Cell Biol. 2009;184:31-44 pubmed publisher
    ..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...
  31. Bonne G, Mercuri E, Muchir A, Urtizberea A, Becane H, Recan D, et al. Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene. Ann Neurol. 2000;48:170-80 pubmed
  32. Colomer J, Iturriaga C, Bonne G, Schwartz K, Manilal S, Morris G, et al. Autosomal dominant Emery-Dreifuss muscular dystrophy: a new family with late diagnosis. Neuromuscul Disord. 2002;12:19-25 pubmed
    ..Clinical, pathological and genetic data are described. We emphasize the difficulties in diagnosis, especially in sporadic cases or young patients in whom the clinical picture is not completely established...
  33. Lammerding J, Hsiao J, Schulze P, Kozlov S, Stewart C, Lee R. Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells. J Cell Biol. 2005;170:781-91 pubmed
  34. Hong J, Ki C, Kim J, Suh Y, Kim J, Baek K, et al. Cardiac dysrhythmias,cardiomyopathy and muscular dystrophy in patients with Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy type 1B. J Korean Med Sci. 2005;20:283-90 pubmed
    ..Cardiologists should know about these unusual genetic diseases with conduction defects, especially in young adults...
  35. Walter M, Witt T, Weigel B, Reilich P, Richard P, Pongratz D, et al. Deletion of the LMNA initiator codon leading to a neurogenic variant of autosomal dominant Emery-Dreifuss muscular dystrophy. Neuromuscul Disord. 2005;15:40-4 pubmed
    ..Thus, the mutation with this unique phenotypical expression represents the first example for a link between the neurogenic and myogenic phenotypes and extends the clinical variability of laminopathies...
  36. Ostlund C, Bonne G, Schwartz K, Worman H. Properties of lamin A mutants found in Emery-Dreifuss muscular dystrophy, cardiomyopathy and Dunnigan-type partial lipodystrophy. J Cell Sci. 2001;114:4435-45 pubmed
    ..These results indicate that some lamin A mutants causing disease can be aberrantly localized, partially disrupt the endogenous lamina and alter emerin localization, whereas others localize normally in transfected cells...
  37. Ellis J, Craxton M, Yates J, Kendrick Jones J. Aberrant intracellular targeting and cell cycle-dependent phosphorylation of emerin contribute to the Emery-Dreifuss muscular dystrophy phenotype. J Cell Sci. 1998;111 ( Pt 6):781-92 pubmed
    ..This data suggests that for emerin to function normally it must be correctly localized, retained at the nuclear membrane and phosphorylated by cell cycle-mediated events...
  38. Vohanka S, Vytopil M, Bednarik J, Lukas Z, Kadanka Z, Schildberger J, et al. A mutation in the X-linked Emery-Dreifuss muscular dystrophy gene in a patient affected with conduction cardiomyopathy. Neuromuscul Disord. 2001;11:411-3 pubmed
    ..This case shows that mutations in X-EMD gene, as it was shown for autosomal-dominant EMD, can cause a predominant cardiac phenotype...
  39. Holmer L, Worman H. Inner nuclear membrane proteins: functions and targeting. Cell Mol Life Sci. 2001;58:1741-7 pubmed
    ..Associations with nuclear ligands retain them in the inner nuclear membrane. Further investigation of the functions and targeting of inner nuclear membrane proteins are needed to determine how they are involved in human disease...
  40. Vytopil M, Ricci E, Dello Russo A, Hanisch F, Neudecker S, Zierz S, et al. Frequent low penetrance mutations in the Lamin A/C gene, causing Emery Dreifuss muscular dystrophy. Neuromuscul Disord. 2002;12:958-63 pubmed
    b>Emery Dreifuss muscular dystrophy is a genetically heterogeneous disorder characterized by the clinical triad of early onset contractures, progressive muscular wasting and weakness with humeroperoneal distribution and cardiac conduction ..
  41. Lee K, Haraguchi T, Lee R, Koujin T, Hiraoka Y, Wilson K. Distinct functional domains in emerin bind lamin A and DNA-bridging protein BAF. J Cell Sci. 2001;114:4567-73 pubmed
  42. Wheeler M, Davies J, Zhang Q, Emerson L, Hunt J, Shanahan C, et al. Distinct functional domains in nesprin-1alpha and nesprin-2beta bind directly to emerin and both interactions are disrupted in X-linked Emery-Dreifuss muscular dystrophy. Exp Cell Res. 2007;313:2845-57 pubmed
  43. Decostre V, Ben Yaou R, Bonne G. Laminopathies affecting skeletal and cardiac muscles: clinical and pathophysiological aspects. Acta Myol. 2005;24:104-9 pubmed
    ..The phenotype of animal models in which the same mutation as that identified in EDMD or DCM-CD patients has been reproduced is presented as well as the pathophysiological mechanisms known to date...
  44. Yates J, Bagshaw J, Aksmanovic V, Coomber E, McMahon R, Whittaker J, et al. Genotype-phenotype analysis in X-linked Emery-Dreifuss muscular dystrophy and identification of a missense mutation associated with a milder phenotype. Neuromuscul Disord. 1999;9:159-65 pubmed
    ..Age at onset was later for first symptoms and for development of ankle contractures and muscle weakness. These findings have diagnostic implications as well as pointing to functionally important regions of the emerin protein...
  45. Fujiita T, Shimizu M, Kaku B, Kanaya H, Horita Y, Uno Y, et al. Abnormal sympathetic innervation of the heart in a patient with Emery-Dreifuss muscular dystrophy. Ann Nucl Med. 2005;19:411-4 pubmed
    ..Six months later, his LV wall motion on echocardiograms developed diffuse hypokinesis. These results suggest that the abnormality on I-123 MIBG myocardial scintigrams may predict LV dysfunction in Emery-Dreifuss muscular dystrophy...
  46. Fidzianska A, Glinka Z. Nuclear architecture remodelling in envelopathies. Folia Neuropathol. 2007;45:47-55 pubmed
    ..All these nuclear aberrations are considered to be structural indicators of nuclear dysfunction evoked by envelope protein deficiency...
  47. Maraldi N, Lattanzi G, Sabatelli P, Ognibene A, Squarzoni S. Functional domains of the nucleus: implications for Emery-Dreifuss muscular dystrophy. Neuromuscul Disord. 2002;12:815-23 pubmed
  48. Quinzii C, Vu T, Min K, Tanji K, Barral S, Grewal R, et al. X-linked dominant scapuloperoneal myopathy is due to a mutation in the gene encoding four-and-a-half-LIM protein 1. Am J Hum Genet. 2008;82:208-13 pubmed publisher
    ..This is the first report, to our knowledge, of X-linked dominant SP myopathy and the first human mutation in FHL1...
  49. Aldwinckle R, Carr A. The anesthetic management of a patient with Emery-Dreifuss muscular dystrophy for orthopedic surgery. Can J Anaesth. 2002;49:467-70 pubmed
  50. Helbling Leclerc A, Bonne G, Schwartz K. Emery-Dreifuss muscular dystrophy. Eur J Hum Genet. 2002;10:157-61 pubmed
    ..The genes known to be responsible for EDMD encode proteins associated with the nuclear envelope: the emerin and the lamins A and C...
  51. Ifergane G, Al Sayed I, Birk O, Harel T, Wirguin I. Co-morbidity of Emery-Dreifuss muscular dystrophy and a congenital myasthenic syndrome possibly affecting the phenotype in a large Bedouin kindred. Eur J Neurol. 2007;14:305-8 pubmed
    ..The superimposed pre-synaptic disorder may have contributed to the development of the neurogenic features demonstrated in these patients...
  52. Liang W, Yuo C, Liu C, Lee C, Goto K, Hayashi Y, et al. Novel LMNA mutation in a Taiwanese family with autosomal dominant Emery-Dreifuss muscular dystrophy. J Formos Med Assoc. 2007;106:S27-31 pubmed
    ..These cases illustrate the necessity of correct diagnosis, evaluation, and follow-up of cardiac problems due to the wide clinical spectrum and high prevalence of cardiac conduction block in patients with autosomal dominant EDMD...
  53. Cuneo A, Holdt L, Klingel K, Kandolf R, Tebbe U. [Cardiologic findings in Hauptmann-Thannhauser muscular dystrophy (autosomal dominant Emery-Dreifuss muscular dystrophy)]. Dtsch Med Wochenschr. 2007;132:2006-9 pubmed
    ..He also developed increasing muscular weakness. Three years before the diagnosis of autosomal-dominant Emery-Dreifuss muscular dystrophy (EDMD) had been made...