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1

Emery-Dreifuss muscular dystrophy  

Microsoft Academic Search

Emery-Dreifuss muscular dystrophy (EDMD) is inherited in an X-linked or autosomal manner. X-linked EDMD is caused by mutations\\u000a in EMD, which encodes an integral protein of the nuclear envelope inner membrane called emerin. Autosomally inherited EDMD is caused\\u000a by mutations in LMNA, which encodes A-type nuclear lamins, intermediate filament proteins associated with inner nuclear membrane. Although the\\u000a causative mutations have

Antoine Muchir; Howard J. Worman

2007-01-01

2

Emery-Dreifuss humeroperoneal muscular dystrophy: cardiac manifestations.  

PubMed

Emery-Dreifuss muscular dystrophy (EDMD) is an inherited disorder affecting skeletal and cardiac muscles and characterized by muscular atrophy, contractures, and cardiomyopathy with conduction defects. It can be X-linked or autosomal. Not all patients with EDMD develop heart involvement, but heart disease associated with EDMD can be unpredictable and may be life threatening. In rare cases heart problems may be the first symptom of EDMD. Early recognition of heart involvement is of utmost importance as placement of a pacemaker and/or defibrillator may be lifesaving. PMID:22480903

Parmar, Malvinder S; Parmar, Kamalpreet S

2012-04-04

3

Orthopedic deformities in Emery-Dreifuss muscular dystrophy.  

PubMed

Orthopedic deformities in Emery-Dreifuss muscular dystrophy are discussed based on a study of four patients and an extensive literature review. The condition is characterized by slowly progressive humeroperoneal muscle weakness; ankle equinus, elbow flexion, and neck extensor muscle contractures; paravertebral muscle tightness; and cardiac abnormalities involving bradycardia and atrioventricular conduction defects. Tendo Achilles lengthening is warranted, since patients remain ambulatory for several decades. Scoliosis occurred in three patients but stabilized in the absence of treatment. Recognition of the condition is important to allow for heart pacemaker insertion because the usually asymptomatic cardiac abnormalities are associated with a high incidence of sudden death in mid-adult life. PMID:2056082

Shapiro, F; Specht, L

4

Emery-Dreifuss muscular dystrophy, laminopathies, and other nuclear envelopathies.  

PubMed

The nuclear envelopathies, more frequently known as laminopathies are a rapidly expanding group of human hereditary diseases caused by mutations of genes that encode proteins of the nuclear envelope. The most frequent and best known form is Emery-Dreifuss muscular dystrophy (EDMD), a skeletal myopathy characterized by progressive muscular weakness, joint contractures, and cardiac disease. EMD gene, encoding emerin, causes the X-linked form of EDMD, while LMNA gene encoding lamins A and C, is responsible for autosomal forms, usually with a dominant transmission. In the last years, the spectrum of conditions has been extraordinarily enlarged, from a congenital muscular dystrophy with severe paralytic or rapidly progressive picture due to de novo mutations in LMNA (L-CMD) to a limb-girdle muscular dystrophy with adult onset and much milder weakness (LGMD1B). LMNA has also been involved in a form of isolated cardiomyopathy associated with cardiac conduction disease and in an axonal form of hereditary neuropathy. Identification of this gene has been reported also in a number of non-neuromuscular disorders including lipodystrophy syndromes and a wide spectrum of premature aging syndromes ranging from mandibuloacral dysplasia to restrictive dermopathy. Mutations in other genes implicated in the processing or maturation of nuclear lamins have also been found. The extraordinary complexity of the molecular and pathophysiological mechanisms of these diseases is still not well known and the occurrence of modifying factors or genes is highly suspected. Identification of new genes and investigation of new therapeutic approaches are in progress. PMID:23622360

Bonne, Gisèle; Quijano-Roy, Susana

2013-01-01

5

Early presentation of X-linked Emery–Dreifuss muscular dystrophy resembling limb-girdle muscular dystrophy  

Microsoft Academic Search

Emery–Dreifuss muscular dystrophy is an X-linked neuromuscular disorder caused by defects in the STA gene on Xq28, which codes for a nuclear protein named emerin. Affected patients usually present in early adolescence with scapulo-peroneal muscle weakness and wasting, and contractures of the tendo Achilles, elbows and paraspinal muscles, resulting in spine rigidity. We present here a case of Emery–Dreifuss muscular

Francesco Muntoni; Ewa J Lichtarowicz-Krynska; Caroline A Sewry; Sushila Manilal; Dominique Recan; Stephane Llense; Jacqueline Taylor; Glenn E Morris; Victor Dubowitz

1998-01-01

6

Modifier locus of the skeletal muscle involvement in Emery–Dreifuss muscular dystrophy  

Microsoft Academic Search

Autosomal dominant Emery–Dreifuss muscular dystrophy is caused by mutations in LMNA gene encoding lamins A and C. The disease is characterized by early onset joint contractures during childhood associated\\u000a with humero-peroneal muscular wasting and weakness, and by the development of a cardiac disease in adulthood. Important intra-familial\\u000a variability characterized by a wide range of age at onset of myopathic symptoms

B. Granger; L. Gueneau; V. Drouin-Garraud; V. Pedergnana; F. Gagnon; R. Ben Yaou; S. Tezenas du Montcel; G. Bonne

2011-01-01

7

Heart-specific localization of emerin: new insights into Emery-Dreifuss muscular dystrophy  

Microsoft Academic Search

Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked inherited disease characterized by early contracture of the elbows, Achilles tendons and post-cervical muscles, slow progressive muscle wasting and weakness and cardiomyopathy presenting with arrhythmia and atrial paralysis: heart block can eventually lead to sudden death. The EDMD gene encodes a novel ubiquitous protein, emerin, which decorates the nuclear rim of many cell

Luca Cartegni; Marina Raffaele; Rita Barresi; Stefano Squarzoni; Patrizia Sabatelli; Nadir Maraldi; Marina Mora; Claudia Di Blasi; Ferdinando Cornelio; Luciano Merlini; Antonello Villa; Fabio Cobianchi; Daniela Toniolo

1997-01-01

8

Multiple roles for emerin: implications for Emery-Dreifuss muscular dystrophy  

PubMed Central

X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) is inherited through mutations in EMD, which encodes a nuclear membrane protein named emerin. Emerin is expressed in most cells, but EDMD strikes specific tissues. This review summarizes growing evidence that emerin has roles in both tissue-specific gene regulation and the mechanical integrity of the nucleus, and discusses how these roles might impact EDMD.

Holaska, James M.; Wilson, Katherine L.

2008-01-01

9

Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy  

PubMed Central

Mutations in LMNA, which encodes nuclear Lamins A and C cause diseases affecting various organs, including the heart. We have determined the effects of an Lmna H222P mutation on signaling pathways involved in the development of cardiomyopathy in a knockin mouse model of autosomal dominant Emery-Dreifuss muscular dystrophy. Analysis of genome-wide expression profiles in hearts using Affymetrix GeneChips showed statistically significant differences in expression of genes in the MAPK pathways at the incipience of the development of clinical disease. Using real-time PCR, we showed that activation of MAPK pathways preceded clinical signs or detectable molecular markers of cardiomyopathy. In heart tissue and isolated cardiomyocytes, there was activation of MAPK cascades and downstream targets, implicated previously in the pathogenesis of cardiomyopathy. Expression of H222P Lamin A in cultured cells activated MAPKs and downstream target genes. 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.

Muchir, Antoine; Pavlidis, Paul; Decostre, Valerie; Herron, Alan J.; Arimura, Takuro; Bonne, Gisele; Worman, Howard J.

2007-01-01

10

Differentiating Emery-Dreifuss muscular dystrophy and collagen VI-related myopathies using a specific CT scanner pattern  

Microsoft Academic Search

Bethlem myopathy and Ullrich congenital muscular dystrophy are part of the heterogeneous group of collagen VI-related muscle disorders. They are caused by mutations in collagen VI (ColVI) genes (COL6A1, COL6A2, and COL6A3) while LMNA mutations cause autosomal dominant Emery-Dreifuss muscular dystrophy. A muscular dystrophy pattern and contractures are found in all three conditions, making differential diagnosis difficult especially in young

N. Deconinck; E. Dion; R. Ben Yaou; A. Ferreiro; B. Eymard; L. Briñas; C. Payan; T. Voit; P. Guicheney; P. Richard; V. Allamand; G. Bonne; T. Stojkovic

2010-01-01

11

The role of the nuclear envelope in Emery-Dreifuss muscular dystrophy.  

PubMed

The X-linked form of Emery-Dreifuss muscular dystrophy (X-EDMD) is caused by absence, or greatly reduced amounts, of the inner nuclear-membrane protein, emerin. The autosomal dominant form (AD-EDMD) is caused by missense mutations in lamins A and C, two components of the nuclear lamina that interact directly with emerin. Lamin A/C mutations also cause one form of dilated cardiomyopathy (CMD1A) and one form of limb-girdle muscular dystrophy (LGMD1B), both of which have clinical features in common with EDMD, as well as a rare, unrelated form of lipodystrophy (FPLD). Evidence is now emerging that defective assembly of the nuclear lamina is a feature of all these diseases, although not necessarily the direct cause. 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. PMID:11733221

Morris, G E

2001-12-01

12

Emery-Dreifuss muscular dystrophy: linkage to markers in distal Xq28.  

PubMed Central

Emery-Dreifuss muscular dystrophy (EMD) is characterised by (1) early contractures of the Achilles tendons, elbows, and postcervical muscles, (2) slowly progressive muscle wasting and weakness with a predominantly humeroperoneal distribution in the early stages, and (3) cardiomyopathy with conduction defects and risk of sudden death. Inheritance is usually X linked recessive but can be autosomal dominant. Family linkage studies have mapped X linked EMD to the distal long arm of the X chromosome but precise genetic localisation has been hampered by the rarity of this condition. We report three new families with X linked Emery-Dreifuss muscular dystrophy studied with DNA markers from Xq27-qter and three previously published families typed for additional markers. No recombination was observed with the red/green cone pigment locus, RGCP (lod score, Z = 2.46), the factor VIII coagulant gene locus, F8C (Z = 6.39), or with DXS115 (Z = 4.94). Two recombinants were observed which mapped EMD distal to DXS15 (DX13) and DXS52 (St14) respectively. Multipoint linkage analysis gave odds exceeding 200:1 for EMD being distal to these markers. A multipoint analysis incorporating published data gave the map cen-DXS304-9cM-DXS15-3cM-DXS52-2 cM-(RGCP,EMD)-3cM-F8C-2cM-DXS115 with odds of 120:1 in favour of a location for EMD between DXS52 and F8C as compared to the next best position distal to F8C.

Yates, J R; Warner, J P; Smith, J A; Deymeer, F; Azulay, J P; Hausmanowa-Petrusewicz, I; Zaremba, J; Borkowska, J; Affara, N A; Ferguson-Smith, M A

1993-01-01

13

Localisation of the gene for Emery-Dreifuss muscular dystrophy to the distal long arm of the X chromosome.  

PubMed Central

The linkage relationships of the gene for Emery-Dreifuss muscular dystrophy have been analysed in a large American kindred using DNA probes from different regions of the X chromosome. Close linkage was found with the locus for factor VIII, with no recombinants in 12 opportunities (maximum lod score 4.3), and with locus DXS15 (two recombinants in 17 opportunities, maximum lod score 2.9 at 0 = 10 cM). No linkage was found with probes pERT87 and 754, which are closely linked to Duchenne and Becker muscular dystrophies at Xp21. These results confirm a separate localisation on the distal part of the long arm at q27-28 for Emery-Dreifuss muscular dystrophy and should provide the basis for prenatal diagnosis and improved carrier detection in this disorder if the linkage is confirmed to be close.

Thomas, N S; Williams, H; Elsas, L J; Hopkins, L C; Sarfarazi, M; Harper, P S

1986-01-01

14

Deletion of the LMNA initiator codon leading to a neurogenic variant of autosomal dominant Emery–Dreifuss muscular dystrophy  

Microsoft Academic Search

Mutations in the LMNA gene encoding the nuclear envelope protein, lamins A and C, have been associated with at least nine distinct disorders now called laminopathies, including Emery–Dreifuss muscular dystrophy and Charcot–Marie–Tooth type 2 disease. We identified a novel mutation in the 5? region of the LMNA gene ?3del15, resulting in the loss of 15 nucleotides from ?3 to +12,

Maggie C. Walter; Thomas N. Witt; Beate Schlotter Weigel; Peter Reilich; Pascale Richard; Dieter Pongratz; Gisèle Bonne; Manfred S. Wehnert; Hanns Lochmüller

2005-01-01

15

Lamin A/C-mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy  

PubMed Central

The LMNA gene encodes lamins A and C, two intermediate filament-type proteins that are important determinants of interphase nuclear architecture. Mutations in LMNA lead to a wide spectrum of human diseases including autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD), which affects skeletal and cardiac muscle. The cellular mechanisms by which mutations in LMNA cause disease have been elusive. Here, we demonstrate that defects in neuromuscular junctions (NMJs) are part of the disease mechanism in AD-EDMD. Two AD-EDMD mouse models show innervation defects including misexpression of electrical activity–dependent genes and altered epigenetic chromatin modifications. Synaptic nuclei are not properly recruited to the NMJ because of mislocalization of nuclear envelope components. AD-EDMD patients with LMNA mutations show the same cellular defects as the AD-EDMD mouse models. 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.

Mejat, Alexandre; Decostre, Valerie; Li, Juan; Renou, Laure; Kesari, Akanchha; Hantai, Daniel; Stewart, Colin L.; Xiao, Xiao; Hoffman, Eric; Bonne, Gisele; Misteli, Tom

2009-01-01

16

Lamin A N-terminal phosphorylation is associated with myoblast activation: impairment in Emery-Dreifuss muscular dystrophy  

PubMed Central

Background: Skeletal muscle disorders associated with mutations of lamin A/C gene include autosomal Emery–Dreifuss muscular dystrophy and limb girdle muscular dystrophy 1B. The pathogenic mechanism underlying these diseases is unknown. Recent data suggest an impairment of signalling mechanisms as a possible cause of muscle malfunction. A molecular complex in muscle cells formed by lamin A/C, emerin, and nuclear actin has been identified. The stability of this protein complex appears to be related to phosphorylation mechanisms. Objective: To analyse lamin A/C phosphorylation in control and laminopathic muscle cells. Methods: Lamin A/C N-terminal phosphorylation was determined in cultured mouse myoblasts using a specific antibody. Insulin treatment of serum starved myoblast cultures was carried out to evaluate involvement of insulin signalling in the phosphorylation pathway. Screening of four Emery–Dreifuss and one limb girdle muscular dystrophy 1B cases was undertaken to investigate lamin A/C phosphorylation in both cultured myoblasts and mature muscle fibres. Results: Phosphorylation of lamin A was observed during myoblast differentiation or proliferation, along with reduced lamin A/C phosphorylation in quiescent myoblasts. Lamin A N-terminus phosphorylation was induced by an insulin stimulus, which conversely did not affect lamin C phosphorylation. Lamin A/C was also hyperphosphorylated in mature muscle, mostly in regenerating fibres. Lamin A/C phosphorylation was strikingly reduced in laminopathic myoblasts and muscle fibres, while it was preserved in interstitial fibroblasts. Conclusions: Altered lamin A/C interplay with a muscle specific phosphorylation partner might be involved in the pathogenic mechanism of Emery–Dreifuss muscular dystrophy and limb girdle muscular dystrophy 1B.

Cenni, V; Sabatelli, P; Mattioli, E; Marmiroli, S; Capanni, C; Ognibene, A; Squarzoni, S; Maraldi, N; Bonne, G; Columbaro, M; Merlini, L; Lattanzi, G

2005-01-01

17

Identification of lamin A\\/C ( LMNA ) gene mutations in Korean patients with autosomal dominant Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy 1B  

Microsoft Academic Search

Mutations in the LMNA gene encoding lamins A and C by alternative splicing have been found to cause at least four different kinds of genetic disorders:\\u000a autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; MIM 181350); limb-girdle muscular dystrophy type 1B (LGMD1B;\\u000a MIM 159001); dilated cardiomyopathy type 1A (CMD1A; MIM 115200); and familial partial lipodystrophy (FPLD; MIM 151660). Recently,\\u000a we have studied

Chang-Seok Ki; Jong Seo Hong; Gyu-Young Jeong; Kyoung Ju Ahn; Kwang-Mo Choi; Duk-Kyung Kim; Jong-Won Kim

2002-01-01

18

Mutations of the FHL1 Gene Cause Emery-Dreifuss Muscular Dystrophy  

PubMed Central

Emery-Dreifuss muscular dystrophy (EDMD) is a rare disorder characterized by early joint contractures, muscular dystrophy, and cardiac involvement with conduction defects and arrhythmias. So far, only 35% of EDMD cases are genetically elucidated and associated with EMD or LMNA gene mutations, suggesting the existence of additional major genes. By whole-genome scan, we identified linkage to the Xq26.3 locus containing the FHL1 gene in three informative families belonging to our EMD- and LMNA-negative cohort. Analysis of the FHL1 gene identified seven mutations, in the distal exons of FHL1 in these families, three additional families, and one isolated case, which differently affect the three FHL1 protein isoforms: two missense mutations affecting highly conserved cysteines, one abolishing the termination codon, and four out-of-frame insertions or deletions. The predominant phenotype was characterized by myopathy with scapulo-peroneal and/or axial distribution, as well as joint contractures, and associated with a peculiar cardiac disease characterized by conduction defects, arrhythmias, and hypertrophic cardiomyopathy in all index cases of the seven families. Heterozygous female carriers were either asymptomatic or had cardiac disease and/or mild myopathy. Interestingly, four of the FHL1-mutated male relatives had isolated cardiac disease, and an overt hypertrophic cardiomyopathy was present in two. Expression and functional studies demonstrated that the FHL1 proteins were severely reduced in all tested patients and that this was associated with a severe delay in myotube formation in the two patients for whom myoblasts were available. In conclusion, FHL1 should be considered as a gene associated with the X-linked EDMD phenotype, as well as with hypertrophic cardiomyopathy.

Gueneau, Lucie; Bertrand, Anne T.; Jais, Jean-Philippe; Salih, Mustafa A.; Stojkovic, Tanya; Wehnert, Manfred; Hoeltzenbein, Maria; Spuler, Simone; Saitoh, Shinji; Verschueren, Annie; Tranchant, Christine; Beuvin, Maud; Lacene, Emmanuelle; Romero, Norma B.; Heath, Simon; Zelenika, Diana; Voit, Thomas; Eymard, Bruno; Ben Yaou, Rabah; Bonne, Gisele

2009-01-01

19

Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy.  

PubMed

Emery-Dreifuss muscular dystrophy (EDMD) is a rare disorder characterized by early joint contractures, muscular dystrophy, and cardiac involvement with conduction defects and arrhythmias. So far, only 35% of EDMD cases are genetically elucidated and associated with EMD or LMNA gene mutations, suggesting the existence of additional major genes. By whole-genome scan, we identified linkage to the Xq26.3 locus containing the FHL1 gene in three informative families belonging to our EMD- and LMNA-negative cohort. Analysis of the FHL1 gene identified seven mutations, in the distal exons of FHL1 in these families, three additional families, and one isolated case, which differently affect the three FHL1 protein isoforms: two missense mutations affecting highly conserved cysteines, one abolishing the termination codon, and four out-of-frame insertions or deletions. The predominant phenotype was characterized by myopathy with scapulo-peroneal and/or axial distribution, as well as joint contractures, and associated with a peculiar cardiac disease characterized by conduction defects, arrhythmias, and hypertrophic cardiomyopathy in all index cases of the seven families. Heterozygous female carriers were either asymptomatic or had cardiac disease and/or mild myopathy. Interestingly, four of the FHL1-mutated male relatives had isolated cardiac disease, and an overt hypertrophic cardiomyopathy was present in two. Expression and functional studies demonstrated that the FHL1 proteins were severely reduced in all tested patients and that this was associated with a severe delay in myotube formation in the two patients for whom myoblasts were available. In conclusion, FHL1 should be considered as a gene associated with the X-linked EDMD phenotype, as well as with hypertrophic cardiomyopathy. PMID:19716112

Gueneau, Lucie; Bertrand, Anne T; Jais, Jean-Philippe; Salih, Mustafa A; Stojkovic, Tanya; Wehnert, Manfred; Hoeltzenbein, Maria; Spuler, Simone; Saitoh, Shinji; Verschueren, Annie; Tranchant, Christine; Beuvin, Maud; Lacene, Emmanuelle; Romero, Norma B; Heath, Simon; Zelenika, Diana; Voit, Thomas; Eymard, Bruno; Ben Yaou, Rabah; Bonne, Gisèle

2009-08-27

20

In Vitro Contracture Test Results and Anaesthetic Management of a Patient with Emery-Dreifuss Muscular Dystrophy for Cardiac Transplantation  

PubMed Central

Emery-Dreifuss muscular dystrophy (EDMD) is a hereditary neuromuscular disorder characterized by slowly progressive muscle weakness, early contractures, and dilated cardiomyopathy. We reported an uneventful general anaesthesia using total intravenous anaesthesia (TIVA) for cardiac transplantation in a 19-year-old woman suffering from EDMD. In vitro contracture test results of two pectoralis major muscle bundles of the patient suggest that exposition to triggering agents does not induce a pathological sarcoplasmic calcium release in the lamin A/C phenotype. However, due to the lack of evidence in the literature, we would recommend TIVA for patients with EDMD if general anaesthesia is required.

Schuster, Frank; Wessig, Carsten; Schimmer, Christoph; Johannsen, Stephan; Lazarus, Marc; Aleksic, Ivan; Leyh, Rainer; Roewer, Norbert

2012-01-01

21

Novel and recurrent EMD mutations in patients with Emery–Dreifuss muscular dystrophy, identify exon 2 as a mutation hot spot  

Microsoft Academic Search

Emery–Dreifuss muscular dystrophy (EDMD) is a neuromuscular disorder exhibiting a cardiomyopathy with cardiac conduction defects. X-linked EDMD arises from mutations in the EMD gene, which encodes for a nuclear membrane protein termed emerin. In this study, we describe novel and recurrent EMD mutations identified in 18 probands and three carriers from a cohort of 255 North American patients referred for

Charlotte A Brown; Juergen Scharner; Kevin Felice; Matthew N Meriggioli; Mark Tarnopolsky; Matthew Bower; Peter S Zammit; Jerry R Mendell; Juliet A Ellis

2011-01-01

22

Pathology and nuclear abnormalities in hearts of transgenic mice expressing M371K lamin A encoded by an LMNA mutation causing Emery-Dreifuss muscular dystrophy  

Microsoft Academic Search

Mutations in LMNA, which encodes nuclear lamins A and C, cause a broad range of diseases, including autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD) and related disorders with a predominant cardiomyopathy. Homozygous Lmna model 'knock-in' and null mice develop cardiomyopathy, whereas het- erozygous mice do not. Overexpression of lamin A mutants that cause cardiomyopathy in cultured cells induces morphological abnormalities in

Yuexia Wang; Alan J. Herron; Howard J. Worman

2006-01-01

23

Expression and localization of nuclear proteins in autosomal-dominant Emery-Dreifuss muscular dystrophy with LMNA R377H mutation  

Microsoft Academic Search

BACKGROUND: The autosomal dominant form of Emery-Dreifuss muscular dystrophy (AD-EDMD) is caused by mutations in the gene encoding for the lamins A and C (LMNA). Lamins are intermediate filament proteins which form the nuclear lamina underlying the inner nuclear membrane. We have studied the expression and the localization of nuclear envelope proteins in three different cell types and muscle tissue

Beate Reichart; Ruth Klafke; Christine Dreger; Eleonora Krüger; Isabell Motsch; Andrea Ewald; Jochen Schäfer; Heinz Reichmann; Clemens R Müller; Marie-Christine Dabauvalle

2004-01-01

24

Homozygous lamin A/C familial lipodystrophy R482Q mutation in autosomal recessive Emery Dreifuss muscular dystrophy.  

PubMed

Autosomal recessive Emery Dreifuss muscular dystrophy (AR-EDMD) is rare, with few reports in the medical literature. We describe the first cases of AR-EDMD and autosomal dominant familial partial lipodystrophy (FPLD) in the Hutterite population resulting from homozygous or heterozygous R482Q mutations in the lamin A/C gene (LMNA). Heterozygosity for LMNA R482Q mutation causes FPLD, which is associated with increased risk of hyperlipidemia and hypertension. The overall carrier frequency of the R482Q mutation in Dariusleut and Leherleut Hutterites in Alberta was found to be 1.45%. Homozygosity for this mutation has not been previously reported and here resulted in a combination of generalized lipodystrophy and EDMD. Knowledge that the LMNA R482Q mutation is present in this population is important for genetic counseling, surveillance, and management of the associated disorders. PMID:23313286

Wiltshire, Katie M; Hegele, Robert A; Innes, A Micheil; Brownell, A Keith W

2013-01-11

25

Activation of MAPK in hearts of EMD null mice: similarities between mouse models of X-linked and autosomal dominant Emery Dreifuss muscular dystrophy  

Microsoft Academic Search

Emery-Dreifuss muscular dystrophy (EDMD) is an inherited disorder characterized by slowly progressive skeletal muscle weakness in a humero-peroneal distribution, early contractures and prominent cardiomyopa- thy with conduction block. Mutations in EMD, encoding emerin, and LMNA, encoding A-type lamins, respecti- vely, cause X-linked and autosomal dominant EDMD. Emerin and A-type lamins are proteins of the inner membrane of the nuclear envelope.

Antoine Muchir; Paul Pavlidis; Gisele Bonne; Yukiko K. Hayashi; Howard J. Worman

2007-01-01

26

Cardiac Dysrhythmias, Cardiomyopathy and Muscular Dystrophy in Patients with Emery-Dreifuss Muscular Dystrophy and Limb-Girdle Muscular Dystrophy Type 1B  

PubMed Central

Emery-Dreifuss muscular dystrophy (EDMD) and limb-girdle muscular dystrophy type 1B (LGMD1B) are characterized by cardiac dysrhythmias, late-onset cardiomyopathy, slowly progressive skeletal myopathy and contractures of the neck, elbows and ankles. The causative mutation is either in the emerin gene (X-linked recessive EDMD) or lamin A/C gene (autosomal dominant EDMD2 or LGMD1B). We report three cases of EDMD, EDMD2 and LGMD1B. A 14-yr-old boy showed limitation of cervical flexion and contractures of both elbows and ankles. Sinus arrest with junctional escape beats was noted. He was diagnosed as X-linked recessive EDMD (MIM 310300). A 28-yr-old female showed severe wasting and weakness of humeroperoneal muscles. Marked limitation of cervical flexion and contractures of both elbows and ankles were noted. Varying degrees of AV block were noted. She was diagnosed as autosomal dominant EDMD2 (MIM 181350). A 41-yr-old female had contractures of both ankles and limb-girdle type muscular dystrophy. ECG revealed atrial tachycardia with high grade AV block. She was diagnosed as autosomal dominant LGMD1B (MIM 159001). Cardiac dysrhythmias in EDMD and LGMD1B include AV block, bradycardia, atrial tachycardia, atrial fibrillation, and atrial standstill, causing sudden death necessitating pacemaker implantation. Cardiologists should know about these unusual genetic diseases with conduction defects, especially in young adults.

Hong, Jong-Seo; Ki, Chang-Seok; Kim, Jong-Won; Suh, Yeon-Lim; Kim, June Soo; Baek, Kyung Kee; Kim, Byoung Joon; Ahn, Kyoung Ju

2005-01-01

27

Dysregulation of FHL1 spliceforms due to an indel mutation produces an Emery-Dreifuss muscular dystrophy plus phenotype.  

PubMed

Emery-Dreifuss muscular dystrophy (EDMD) is characterised by early-onset joint contractures, progressive muscular weakness and wasting and late-onset cardiac disease. 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. Here, we identify a three-generation family with an extended EDMD phenotype due to a novel indel mutation in FHL1 that differentially affects the relative expression of the three known transcript isoforms produced from this locus. The additional phenotypic manifestations in this family-proportionate short stature, facial dysmorphism, pulmonary valvular stenosis, thoracic scoliosis, brachydactyly, pectus deformities and genital abnormalities-are reminiscent of phenotypes seen with dysregulated Ras-mitogen-activated protein kinase (RAS-MAPK) signalling [Noonan syndrome (NS) and related disorders]. The misexpression of FHL1 transcripts precipitated by this mutation, together with the role of FHL1 in the regulation of RAS-MAPK signalling, suggests that this mutation confers a complex phenotype through both gain- and loss-of-function mechanisms. This indel mutation in FHL1 broadens the spectrum of FHL1-related disorders and implicates it in the pathogenesis of NS spectrum disorders. PMID:23456229

Tiffin, Heather R; Jenkins, Zandra A; Gray, Mary J; Cameron-Christie, Sophia R; Eaton, Jennifer; Aftimos, Salim; Markie, David; Robertson, Stephen P

2013-03-02

28

Identification of lamin A/C ( LMNA) gene mutations in Korean patients with autosomal dominant Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy 1B.  

PubMed

Mutations in the LMNA gene encoding lamins A and C by alternative splicing have been found to cause at least four different kinds of genetic disorders: autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2; MIM 181350); limb-girdle muscular dystrophy type 1B (LGMD1B; MIM 159001); dilated cardiomyopathy type 1A (CMD1A; MIM 115200); and familial partial lipodystrophy (FPLD; MIM 151660). Recently, we have studied two Korean patients with atrioventricular conduction defects. They had variable extents of muscular dystrophy; one patient was diagnosed with EDMD2 and the other with LGMD1B. We performed a mutation analysis of the LMNA gene by direct sequencing and found two different missense mutations: R249Q and R377L, in the EDMD2 and LGMD1B patient, respectively. The R249Q mutation is located within the central rod domain of the LMNA gene, and has been described in at least five unrelated sporadic EDMD2 patients. On the other hand, the R377L mutation, also located within the rod domain, is a novel mutation, although a histidine substitution instead of leucine (R377H) has been reported previously in an LGMD1B patient. To our knowledge, this is the first report of LMNA gene mutations in Korean patients with EDMD2 and LGMD1B. PMID:12032588

Ki, Chang-Seok; Hong, Jong Seo; Jeong, Gyu-Young; Ahn, Kyoung Ju; Choi, Kwang-Mo; Kim, Duk-Kyung; Kim, Jung-Won

2002-01-01

29

Functions and dysfunctions of the nuclear lamin Ig-fold domain in nuclear assembly, growth, and Emery-Dreifuss muscular dystrophy  

PubMed Central

The non-?-helical C terminus of Xenopus lamin B3 (LB3T) inhibits the polymerization of lamin B3 in vitro and prevents the assembly of nuclei in Xenopus egg interphase extracts. To more precisely define the functions of LB3T in nuclear assembly, we have expressed subdomains of LB3T and determined their effects on nuclear assembly in Xenopus extracts. The results demonstrate that the Ig-fold motif (LB3T-Ig) is sufficient to inhibit lamin polymerization in vitro. Addition of the LB3T-Ig to egg extracts before the introduction of chromatin prevents chromatin decondensation and the assembly of the lamina, membranes, and pore complexes comprising the nuclear envelope. When added to assembled nuclei, LB3T-Ig prevents the further incorporation of lamin B3 into the endogenous lamina and blocks nuclear growth. The introduction of a point mutation in LB3T-Ig (R454W; LB3T-IgRW), known to cause Emery–Dreifuss muscular dystrophy when present in lamin A, does not inhibit lamin polymerization, chromatin decondensation, or nuclear assembly and growth. These results shed light on the specific alterations in lamin functions attributable to a known muscular dystrophy mutation and provide an experimental framework for revealing the effects of other mutations causing a wide range of laminopathies.

Shumaker, Dale K.; Lopez-Soler, Reynold I.; Adam, Stephen A.; Herrmann, Harald; Moir, Robert D.; Spann, Timothy P.; Goldman, Robert D.

2005-01-01

30

Expression of a Mutant Lamin A That Causes Emery-Dreifuss Muscular Dystrophy Inhibits In Vitro Differentiation of C2C12 Myoblasts  

PubMed Central

Autosomal dominantly inherited missense mutations in lamins A and C cause several tissue-specific diseases, including Emery-Dreifuss muscular dystrophy (EDMD) and Dunnigan-type familial partial lipodystrophy (FPLD). Here we analyze myoblast-to-myotube differentiation in C2C12 clones overexpressing lamin A mutated at arginine 453 (R453W), one of the most frequent mutations in EDMD. In contrast with clones expressing wild-type lamin A, these clones differentiate poorly or not at all, do not exit the cell cycle properly, and are extensively committed to apoptosis. These disorders are correlated with low levels of expression of transcription factor myogenin and with the persistence of a large pool of hyperphosphorylated retinoblastoma protein. Since clones mutated at arginine 482 (a site responsible for FPLD) differentiate normally, we conclude that C2C12 clones expressing R453W-mutated lamin A represent a good cellular model to study the pathophysiology of EDMD. Our hypothesis is that lamin A mutated at arginine 453 fails to build a functional scaffold and/or to maintain the chromatin compartmentation required for differentiation of myoblasts into myocytes.

Favreau, Catherine; Higuet, Dominique; Courvalin, Jean-Claude; Buendia, Brigitte

2004-01-01

31

Effects of expressing lamin A mutant protein causing Emery-Dreifuss muscular dystrophy and familial partial lipodystrophy in HeLa cells.  

PubMed

Patients with the autosomal dominant form of Emery-Dreifuss muscular dystrophy (EDMD) or familial partial lipodystrophy (FPLD) have specific mutations in the lamin A gene. Three such point mutations, G465D (FPLD), R482L, (FPLD), or R527P (EDMD), were introduced by site-specific mutagenesis in the C-terminal tail domain of a FLAG-tagged full-length lamin A construct. HeLa cells were transfected with mutant and wild-type constructs. Lamin A accumulated in nuclear aggregates and the number of cells with aggregates increased with time after transfection. At 72 h post transfection 60-80% of cells transfected with the mutant lamin A constructs had aggregates, while only 35% of the cells transfected with wild-type lamin A revealed aggregates. Mutant transfected cells expressed 10-24x, and wild-type transfected cells 20x, the normal levels of lamin A. Lamins C, B1 and B2, Nup153, LAP2, and emerin were recruited into aggregates, resulting in a decrease of these proteins at the nuclear rim. Aggregates were also characterized by electron microscopy and found to be preferentially associated with the inner nuclear membrane. Aggregates from mutant constructs were larger than those formed by the wild-type constructs, both in immunofluorescence and electron microscopy. The combined results suggest that aggregate formation is in part due to overexpression, but that there are also mutant-specific effects. PMID:12729796

Bechert, Kim; Lagos-Quintana, Mariana; Harborth, Jens; Weber, Klaus; Osborn, Mary

2003-05-15

32

Expression of a mutant lamin A that causes Emery-Dreifuss muscular dystrophy inhibits in vitro differentiation of C2C12 myoblasts.  

PubMed

Autosomal dominantly inherited missense mutations in lamins A and C cause several tissue-specific diseases, including Emery-Dreifuss muscular dystrophy (EDMD) and Dunnigan-type familial partial lipodystrophy (FPLD). Here we analyze myoblast-to-myotube differentiation in C2C12 clones overexpressing lamin A mutated at arginine 453 (R453W), one of the most frequent mutations in EDMD. In contrast with clones expressing wild-type lamin A, these clones differentiate poorly or not at all, do not exit the cell cycle properly, and are extensively committed to apoptosis. These disorders are correlated with low levels of expression of transcription factor myogenin and with the persistence of a large pool of hyperphosphorylated retinoblastoma protein. Since clones mutated at arginine 482 (a site responsible for FPLD) differentiate normally, we conclude that C2C12 clones expressing R453W-mutated lamin A represent a good cellular model to study the pathophysiology of EDMD. Our hypothesis is that lamin A mutated at arginine 453 fails to build a functional scaffold and/or to maintain the chromatin compartmentation required for differentiation of myoblasts into myocytes. PMID:14749366

Favreau, Catherine; Higuet, Dominique; Courvalin, Jean-Claude; Buendia, Brigitte

2004-02-01

33

Expression and localization of nuclear proteins in autosomal-dominant Emery-Dreifuss muscular dystrophy with LMNA R377H mutation  

PubMed Central

Background The autosomal dominant form of Emery-Dreifuss muscular dystrophy (AD-EDMD) is caused by mutations in the gene encoding for the lamins A and C (LMNA). Lamins are intermediate filament proteins which form the nuclear lamina underlying the inner nuclear membrane. We have studied the expression and the localization of nuclear envelope proteins in three different cell types and muscle tissue of an AD-EDMD patient carrying a point mutation R377H in the lamin A/C gene. Results Lymphoblastoid cells, skin fibroblasts, primary myoblasts and muscle thin sections were studied by immunocytochemistry and electron microscopy. Cellular levels of A-type lamins were reduced compared to control cells. In contrast, the amount of emerin and lamin B appeared unaltered. Cell synchronization experiments showed that the reduction of the cellular level of A-type lamin was due to instability of lamin A. By electron microscopy, we identified a proportion of nuclei with morphological alterations in lymphoblastoid cells, fibroblasts and mature muscle fibres. Immunofluorescence microscopy showed that a major population of the lamin B receptor (LBR), an inner nuclear membrane protein, was recovered in the cytoplasm in association with the ER. In addition, the intranuclear organization of the active form of RNA polymerase II was markedly different in cells of this AD-EDMD patient. This aberrant intranuclear distribution was specifically observed in muscle cells where the pathology of EDMD predominates. Conclusions From our results we conclude: Firstly, that structural alterations of the nuclei which are found only in a minor fraction of lymphoblastoid cells and mature muscle fibres are not sufficient to explain the clinical pathology of EDMD; Secondly, that wild type lamin A is required not only for the retention of LBR in the inner nuclear membrane but also for a correct localization of the transcriptionally active RNA pol II in muscle cells. We speculate that a rearrangement of the internal chromatin could lead to muscle-specific disease symptoms by interference with proper mRNA transcription.

Reichart, Beate; Klafke, Ruth; Dreger, Christine; Kruger, Eleonora; Motsch, Isabell; Ewald, Andrea; Schafer, Jochen; Reichmann, Heinz; Muller, Clemens R; Dabauvalle, Marie-Christine

2004-01-01

34

[Proximal muscular dystrophy with contractures and malignant course: is it a variant of Emery-Dreifuss disease?].  

PubMed

The authors relate a unique observation of the familial form of proximal myodystrophy with early contractures and malignant course. The primary character of muscular injury was confirmed on electromyography. The data of electrocardiography and echocardiography attested to the presence in the patients of the signs of cardiomyopathy. Since the disease was diagnosed in 3 brothers, the X-coupled recessive type of its inheritance is assumed. An opinion is advanced that the described form is a clinical variety of Emery-Dreyfus myodystrophy. PMID:2163170

Badalian, L o; Temin, P A; Kalinin, V A; Arkhipov, B A; Zabadenko, N N; Voloshina, T G; Lysov, V L

1990-01-01

35

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.  

PubMed

Autosomal dominantly inherited missense mutations in lamins A and C cause familial partial lipodystrophy of the Dunnigan-type (FPLD), and myopathies including Emery-Dreifuss muscular dystrophy (EDMD). While mutations responsible for FPLD are restricted to the carboxyl-terminal tails, those responsible for EDMD are spread throughout the molecules. We observed here the same structural abnormalities in the nuclear envelope and chromatin of fibroblasts from patients with FPLD and EDMD, harboring missense mutations at codons 482 and 453, respectively. Similar nuclear alterations were generated in fibroblasts, myoblasts, and preadipocytes mouse cell lines overexpressing lamin A harboring either of these two mutations. A large variation in sensitivity to lamin A overexpression was observed among the three cell lines, which was correlated with their variable endogenous content in A-type lamins and emerin. The occurrence of nuclear abnormalities was reduced when lamin B1 was coexpressed with mutant lamin A, emphasizing the functional interaction of the two types of lamins. Transfected cells therefore develop similar phenotypes when expressing lamins mutated in the carboxyl-terminal tail at sites responsible for FPLD or EDMD. PMID:12490190

Favreau, Catherine; Dubosclard, Emmanuelle; Ostlund, Cecilia; Vigouroux, Corinne; Capeau, Jacqueline; Wehnert, Manfred; Higuet, Dominique; Worman, Howard J; Courvalin, Jean-Claude; Buendia, Brigitte

2003-01-01

36

The nuclear envelope, muscular dystrophy and gene expression  

Microsoft Academic Search

Lamins and other nuclear envelope proteins organize nuclear architecture through structural attachments that vary dynamically during the cell cycle and cell differentiation. 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. A mouse model for this rare disease has been created by knocking out the gene

Katherine L Wilson

2000-01-01

37

Congenital muscular dystrophy with rigid spine syndrome: A clinical, pathological, radiological, and genetic study  

Microsoft Academic Search

Rigid spine syndrome is a term first proposed by Dubowitz to describe a subset of patients affected by myopathy with early spinal contractures as a prominent feature. While spinal rigidity is a nonspecific feature, found in Emery-Dreifuss muscular dystrophy and in some congenital myopathies, it is also a prominent feature in a group of patients with merosin-positive congenital muscular dystrophy,

Kevin M. Flanigan; Lynne Kerr; Mark B. Bromberg; Claire Leonard; Jay Tsuruda; Ping Zhang; Ronald Cohn; Kevin P. Campbell; Mark Leppert

2000-01-01

38

An Indian family with an Emery-Dreifuss myopathy and familial dilated cardiomyopathy due to a novel LMNA mutation  

PubMed Central

Emery-Dreifuss myopathy can be associated with a cardiomyopathy and cardiac dysrhythmias. The inheritance pattern of Emery-Dreifuss muscular dystrophy (EDMD) is X linked, whereas EDMD2 is autosomal dominant. EDMD2 is caused by lamin A/C gene (LMNA) mutations that produce alterations in the lamin proteins that are integral to nuclear and cell integrity. A 53-year-old man was brought to us with a right internal carotid artery dissection. Detailed work-up of the patient and family members revealed some unusual features, and genetic sequencing of the LMNA gene was undertaken. A novel mutation was identified in two of the samples sent for analysis. We present the first Indian family of EDMD2 with familial dilated cardiomyopathy and cardiac dysrhythmias in whom LMNA gene sequencing was performed. A novel mutation was identified and additional unusual clinical features were described.

Jadhav, Khushal B.; Karpe, Kedarnath K.; Maramattom, Boby V.

2012-01-01

39

The nuclear muscular dystrophies.  

PubMed

Nuclear muscular dystrophies are referred to as inherited muscular dystrophies caused by mutations in genes--(STA) or lamina (LMNA)--encoding components of the nuclear envelope. Phenotypically, they present as Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscle dystrophy 1B (LGMD1B), or dilated cardiomyopathy with conduction defects (DCM-CD). Genetically related are the Dunnigan-type of familial partial lipodystrophy (FPLD) and Charcot-Marie-Tooth neuropathy type 2 (CMT2B). Until now, approximately 70 unique STA mutations, leading to X-linked EDMD or DCM-CD, have resulted mostly in a complete lack of emerin. Further 50 mostly missense mutations in LMNA result in autosomal-dominant EDMD, autosomal-recessive EDMD, LGMD1B, DCM-CD, FPLD, or CMT2B. Independent of type or location of the mutations, emerinopathies and laminopathies show wide clinical intrafamilial and interfamilial variability. Although structural abnormalities of nuclei in animal and cell models have been observed, the molecular pathology of the nuclear muscular dystrophies needs still to be elucidated. PMID:12138994

Wehnert, Manfred S; Bonne, Giséle

2002-06-01

40

Ultrastructural abnormality of sarcolemmal nuclei in Emery-Dreifuss muscular dystrophy (EDMD)  

Microsoft Academic Search

We performed ultrastructural studies on nuclear abnormalities in biopsied muscles from seven patients with EDMD, of three non-related families, and two sporadic cases. The diagnosis was based on clinical data and molecular findings. We detected different degrees of abnormalities in the sarcolemmal nuclei ranging from marked condensation of chromatin to complete damage of nuclear components. Other nuclei in the same

A Fidzia?ska; D Toniolo; I Hausmanowa-Petrusewicz

1998-01-01

41

Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies  

Microsoft Academic Search

Laminopathies are a group of disorders caused by mutations in the LMNA gene encoding A-type lamins, components of the nuclear lamina. Three of these disorders affect specifically the skeletal and\\/or cardiac muscles, and their pathogenic mechanisms are still unknown. We chose the LMNA H222P missense mutation identified in a family with autosomal dominant Emery-Dreifuss muscular dystrophy, one of the striated

Takuro Arimura; Anne Helbling-Leclerc; Catherine Massart; Shaida Varnous; Florence Niel; Emmanuelle Lacene; Yves Fromes; Marcel Toussaint; Anne-Marie Mura; Dagmar I. Keller; Helge Amthor; Richard Isnard; Marie Malissen; Ketty Schwartz; Gisele Bonne

2004-01-01

42

[Cardiac manifestations of muscular dystrophies].  

PubMed

Muscular dystrophies (MD) are a clinically and genetically heterogeneous disease group. In the last few years, remarkable progress has been made in understanding the close und various relations between skeletal muscle disease and heart muscle disease. Cardiac involvement has been documented in a number of primary MDs and is even the dominant feature in some of them. The myocardium can be affected in the form of a dilated cardiomyopathy while the conduction system can be affected resulting in arrhythmias and conduction defects. Many patients with MD die because of cardiac complications like sudden cardiac death or congestive heart failure. Detailed clinical data about cardiac involvement are available for Duchenne/Becker MD, Emery-Dreifuss MD, myotonic dystrophy, and the different limb girdle MDs. Cardiac manifestations were also found in congenital MD, central core disease, proximal myotonic myopathy, and nemaline myopathy. No data about cardiac abnormalities are available in oculopharyngeal MD and rippling muscle disease. The heart of patients with primary MD should be carefully investigated because of the life-threatening events caused by cardiac complications. There is a strong need for a close collaboration between neurologists and cardiologists in order to provide optimal disease management for the affected patients. PMID:15868359

Perrot, A; Spuler, S; Geier, C; Dietz, R; Osterziel, K J

2005-05-01

43

The A-type lamins: nuclear structural proteins as a focus for muscular dystrophy and cardiovascular diseases.  

PubMed

Mutations in the lamin A (LMNA) gene are associated with the tissue-specific diseases Emery-Dreifuss muscular dystrophy (EDMD), limb girdle muscular dystrophy (LGMD-1B), dilated cardiomyopathy with conduction system disease (DCM-CD), and Dunnigan's familial partial lipodystrophy (FPLD). Lamins A and C, the products of the LMNA gene, are nuclear intermediate filament proteins and are the major structural components of the lamina network that underlies and supports the nuclear envelope. Nuclear fragility and mislocalization of the nuclear envelope protein emerin are two defects induced by a lack of the A-type lamins. These observations reveal that organization and structural integrity of the nucleus are critical factors in the origins of certain dystrophic and cardiovascular diseases. PMID:11709282

Mounkes, L C; Burke, B; Stewart, C L

2001-10-01

44

Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb-MyoD pathways in muscle regeneration  

Microsoft Academic Search

Mutations of lamin A\\/C (LMNA) cause a wide range of human disorders, including progeria, lipodystrophy, neuropathies and autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD). EDMD is also caused by X-linked recessive loss-of-function mutations of emerin, another component of the inner nuclear lamina that directly interacts with LMNA. One model for disease pathogenesis of LMNA and emerin mutations is cell- specific perturbations

Marina Bakay; Zuyi Wang; Gisela Melcon; Louis Schiltz; Jianhua Xuan; Po Zhao; Vittorio Sartorelli; Jinwook Seo; Elena Pegoraro; Corrado Angelini; Ben Shneiderman; Diana Escolar; Yi-Wen Chen; Sara T. Winokur; Lauren M. Pachman; Chenguang Fan; Raul Mandler; Yoram Nevo; Erynn Gordon; Yitan Zhu; Yibin Dong; Yue Wang; Eric P. Hoffman

2006-01-01

45

Direct effects of the pathogenic mutation on satellite cell function in muscular dystrophy.  

PubMed

Skeletal muscle is maintained and repaired by resident stem cells called muscle satellite cells, but there is a gradual failure of this process during the progressive skeletal muscle weakness and wasting that characterises muscular dystrophies. The pathogenic mutation causes muscle wasting, but in conditions including Duchenne muscular dystrophy, the mutant gene is not expressed in satellite cells, and so muscle maintenance/repair is not directly affected. The chronic muscle wasting, however, produces an increasingly hostile micro-environment in dystrophic muscle. This probably combines with excessive satellite cell use to eventually culminate in an indirect failure of satellite cell-mediated myofibre repair. By contrast, in disorders such as Emery-Dreifuss muscular dystrophy, the pathogenic mutation not only instigates muscle wasting, but could also directly compromise satellite cell function, leading to less effective muscle homeostasis. This may again combine with excessive use and a hostile environment to further compromise satellite cell performance. Whichever the mechanism, the ultimate consequence of perturbed satellite cell activity is a chronic failure of myofibre maintenance in dystrophic muscle. Here, we review whether the pathogenic mutation can directly contribute to satellite cell dysfunction in a number of muscular dystrophies. PMID:20546725

Morgan, Jennifer E; Zammit, Peter S

2010-05-28

46

Muscular dystrophy in the mdx mouse: histopathology of the soleus and extensor digitorum longus muscles.  

PubMed

We have used light microscopic histomorphometry to quantify the developmental histopathological changes induced by muscular dystrophy in the soleus and extensor digitorum longus (EDL) muscles of the mdx mouse. We find that this X-linked disease exhibits early fibre necrosis with foci of invasive cells, clustering of affected fibres, hyaline fibres, and, in the mixed soleus muscle, a progressive increase in the proportion of type 1 fibres, the mdx soleus containing 58 +/- 5% type 1 fibres by 26 weeks, compared with 27 +/- 4% in control C57BL/10 ScSn mice. This increase is not due to atrophy or slow axon reinnervation of type 2 fibres. Although only 5% of all original fibres survive by 26 weeks in the EDL, the diseased mdx fibres are continuously and successfully replaced by new fibres with internal nuclei, the affected mice thus avoiding the end-stage histopathology and physical disability characteristic of the X-linked human Duchenne and Emery-Dreifuss muscular dystrophies. Homozygous mdx mice share the life expectancy of normal C57BL/10 mice and appear behaviourly normal. The mdx mouse is therefore an excellent mammalian model in which to study the processes of muscle fibre degeneration and regeneration. PMID:3612180

Carnwath, J W; Shotton, D M

1987-08-01

47

Evaluation of Limb-Girdle Muscular Dystrophy  

ClinicalTrials.gov

Becker Muscular Dystrophy; Limb-Girdle Muscular Dystrophy, Type 2A (Calpain-3 Deficiency); Limb-Girdle Muscular Dystrophy, Type 2B (Miyoshi Myopathy, Dysferlin Deficiency); Limb-Girdle Muscular Dystrophy, Type 2I (FKRP-deficiency)

2013-01-10

48

[Amyloidosis in muscular dystrophy].  

PubMed

Mutations in the gene encoding dysferlin (DYSF) cause limb-girdle muscular dystrophy 2B (LGMD2B) and Miyoshi myopathy (MM). We were able to examine eight patients suspected of LGMD2B clinically, histochemically. The genotype was determined in every case. We found sarcolemmal and interstitial amyloid deposits in four muscle sections. All of the mutations associated with amyloid were located in the N-terminal region of dysferlin, and dysferlin clearly proved to be a component of the amyloid deposits. Dysferlin-deficient muscular dystrophy is the first muscular dystrophy in which amyloidosis is involved. This fact must be considered in the process of developing therapeutic strategies. The influence of the amyloid deposits on the pathogenesis of the disease and the possible involvement of other organs in the progressive course are as yet unclear. PMID:19326120

Carl, M; Röcken, C; Spuler, S

2009-05-01

49

Fatigue in muscular dystrophies  

PubMed Central

Fatigue is a frequent complaint in muscular dystrophies but it is yet not well defined or studied. We have examined the issue of muscle fatigue in a series of molecularly defined muscular dystrophies. A greater fatigability is seen in muscular dystrophy patients and can be an acute or chronic status. In Duchenne Muscular Dystrophy and beta-sarcoglycanopathy besides the alteration of dystrophin and/or sarcoglycan complex, a neuronal nitric oxide synthase depletion is frequently found and might correlate with post-exercise fatigability as well as with cardiac involvement. Therefore, it might be an important modulating factor of the severity of myopathy. In myotonic dystrophy, fatigue is a common complaint: muscle is involved and type 1 atrophy is a frequent feature; brain involvement and depressed mood might likely explain the extent of fatigue and daytime sleepiness commonly observed in these patients. Furthermore, in our observation in a series of 24 cases, muscle and brain can be independently involved in DM1 patients. These observations have profound impact on the type of physical therapy to be prescribed in such patients.

Angelini, Corrado; Tasca, Elisabetta

2012-01-01

50

FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY  

PubMed Central

SUMMARY Facioscapulohumeral muscular dystrophy (FSHD), a dominantly inherited disorder, is the third most common dystrophy after Duchenne and myotonic muscular dystrophy. No known effective treatments exist for FSHD. The lack of an understanding of the underlying pathophysiology remains an obstacle in the development of targeted therapeutic interventions. The genetic defect is a loss of a critical number of a repetitive element (D4Z4) in the 4q subtelomeric region. The loss of the repeats results in specific changes in chromatin, structure, although neither the molecular nor the cellular consequences of this change are known. Nevertheless, these epigenetic changes in chromatic structure offer a potential therapeutic target. The following chapter discusses current management strategies in FSHD as well as potential therapeutic interventions to slow down or reverse the progressive muscle atrophy and weakness.

Tawil, Rabi

2008-01-01

51

Muscular dystrophies and other genetic myopathies.  

PubMed

With advances in the genetics of muscle disease, the term, muscular dystrophy, has expanded to include mutations in an increasing large list of genes. This review discusses the genetics, pathophysiology, and potential treatments of the most common forms of muscular dystrophy: Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. Other forms of muscular dystrophy and other genetic muscle disorders are also discussed to provide an overview of this complex clinical problem. PMID:24176421

Shieh, Perry B

2013-11-01

52

Congenital Muscular Dystrophy in Jordanian Children  

Microsoft Academic Search

This is a consecutive study on 28 patients who have been diagnosed as having congenital muscular dystrophy at Jordan University Hospital in the period from January 1990 to February 1997. Of 75 patients diagnosed as having muscle disease, 55 (73.3%) had muscular dystrophy. Of 55 muscular dystrophy patients, 28 (50.9%) had congenital muscular dystrophy, 11 (20%) had Duchenne muscular dystrophy,

Abdelkarim A. Al-Qudah; Musleh Tarawneh

1998-01-01

53

Therapeutic advances in muscular dystrophy.  

PubMed

The muscular dystrophies comprise a heterogeneous group of genetic disorders that produce progressive skeletal muscle weakness and wasting. There has been rapid growth and change in our understanding of these disorders in recent years, and advances in basic science are being translated into increasing numbers of clinical trials. This review will discuss therapeutic developments in 3 of the most common forms of muscular dystrophy: Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. Each of these disorders represents a different class of genetic disease (monogenic, epigenetic, and repeat expansion disorders), and the approach to therapy addresses the diverse and complex molecular mechanisms involved in these diseases. The large number of novel pharmacologic agents in development with good biologic rationale and strong proof of concept suggests there will be an improved quality of life for individuals with muscular dystrophy. Ann Neurol 2013;74:404-411. PMID:23939629

Leung, Doris G; Wagner, Kathryn R

2013-09-01

54

Orocaecal transit time in Duchenne muscular dystrophy.  

PubMed Central

Smooth muscle degeneration may occur in Duchenne muscular dystrophy. We measured fasting orocaecal transit time in patients with advanced Duchenne muscular dystrophy and other muscular dystrophies and in healthy controls. No significant differences were found. In contrast to reports of gastric hypomotility in Duchenne muscular dystrophy, we found no evidence of impaired small intestinal motility.

Korman, S H; Bar-Oz, B; Granot, E; Meyer, S

1991-01-01

55

Overview of the muscular dystrophies.  

PubMed

The muscular dystrophies are a clinically and genetically heterogeneous group of myopathies typically associated with progressive weakness. Weakness may be noted at birth or develop in late adult life. Some patients manifest with myalgias, rhabdomyolysis, or only raised serum creatine kinase levels without any symptoms or signs of weakness. The muscular dystrophies can be inherited in an X-linked, autosomal recessive, or autosomal dominant fashion and can result from mutations affecting structural proteins localizable to the sarcolemmal proteins, nuclear membrane, basement membrane, sarcomere, or nonstructural enzymatic proteins. This chapter provided a brief overview of the muscular dystrophies before later chapters discuss the individual subtypes in greater detail. PMID:21496621

Amato, Anthony A; Griggs, Robert C

2011-01-01

56

Muscular Dystrophy, incurability, eugenics  

PubMed Central

Summary The medical entity “muscular dystrophy” has been the object of a recent opinion campaign aimed at promoting a law in favour of euthanasia. This disease has become, in the eyes of the public, a media model of a particularly severe and incurable disease. This very widespread statement does not correspond to reality as far as concerns the life of these patients, to the condition that they have benefited from a very useful and fully provided empirical treatment. As already seen, the hope for life has already doubled, without clear limits. The idea of inducing an interruption when at death’s door, as long as a systematic prevention prior to birth, does not conform with the motivated opinion of the majority of patients consulted. On the contrary, the dogma of incurability may lead to dramatic individual consequences which should be stressed, from a medical viewpoint, on account of the unacceptable risks of social injustice or eugenics that this would imply.

Rideau, Y; Rideau, F

2007-01-01

57

Limb-girdle muscular dystrophies  

MedlinePLUS

... in which there is muscle weakness and wasting (muscular dystrophy). In most cases, both parents must pass on the non-working (defective) gene for a child to have the disease (autosomal recessive disorder). However, ...

58

Therapeutic approaches to muscular dystrophy  

PubMed Central

Muscular dystrophies are a heterogeneous group of genetic disorders characterized by muscle weakness and wasting. Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy, and although the molecular mechanisms of the disease have been extensively investigated since the discovery of the gene in 1986, there is currently no effective treatment. However, new gene-based therapies have recently emerged with particular noted advances in using conventional gene replacement strategies, RNA-based technology and pharmacological approaches. While the proof of principle has been demonstrated in animal models, several clinical trials have recently been undertaken to investigate the feasibility of these strategies in patients. In particular, antisense-mediated exon skipping has shown encouraging results and holds promise for the treatment of dystrophic muscle. Here, we summarize the recent progress in therapeutic approaches to muscular dystrophies, with an emphasis on gene therapy and exon skipping for DMD.

Goyenvalle, Aurelie; Seto, Jane T.; Davies, Kay E.; Chamberlain, Jeffrey

2011-01-01

59

Alternative splicing and muscular dystrophy  

PubMed Central

Alternative splicing of pre-mRNAs is a major contributor to proteomic diversity and to the control of gene expression in higher eukaryotic cells. For this reasons, alternative splicing is tightly regulated in different tissues and developmental stages and its disruption can lead to a wide range of human disorders. The aim of this review is to focus on the relevance of alternative splicing for muscle function and muscle disease. We begin by giving a brief overview of alternative splicing, muscle-specific gene expression and muscular dystrophy. Next, to illustrate these concepts we focus on two muscular dystrophy, myotonic muscular dystrophy and facioscapulohumeral muscular dystrophy, both associated to disruption of splicing regulation in muscle.

Pistoni, Mariaelena; Ghigna, Claudia; Gabellini, Davide

2013-01-01

60

Translational Research for Muscular Dystrophy.  

National Technical Information Service (NTIS)

The goal of this work is to increase the availability of critical mouse models of human muscular dystrophy (MD) for both hypothesis testing and preclinical therapy development. Our multi-disciplinary team from The Jackson Laboratory (JAX) and the Children...

G. A. Cox

2012-01-01

61

Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies.  

PubMed

Laminopathies are a group of disorders caused by mutations in the LMNA gene encoding A-type lamins, components of the nuclear lamina. Three of these disorders affect specifically the skeletal and/or cardiac muscles, and their pathogenic mechanisms are still unknown. 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. The mutant mice exhibit overtly normal embryonic development and sexual maturity. At adulthood, male homozygous mice display reduced locomotion activity with abnormal stiff walking posture and all of them die by 9 months of age. As for cardiac phenotype, they develop chamber dilation and hypokinesia with conduction defects. These abnormal skeletal and cardiac features were also observed in the female homozygous mice but with a later-onset than in males. Histopathological analysis of the mice revealed muscle degeneration with fibrosis associated with dislocation of heterochromatin and activation of Smad signalling in heart and skeletal muscles. 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. PMID:15548545

Arimura, Takuro; Helbling-Leclerc, Anne; Massart, Catherine; Varnous, Shaida; Niel, Florence; Lacène, Emmanuelle; Fromes, Yves; Toussaint, Marcel; Mura, Anne-Marie; Keller, Dagmar I; Amthor, Helge; Isnard, Richard; Malissen, Marie; Schwartz, Ketty; Bonne, Gisèle

2004-11-17

62

Diagnosis and new treatments in muscular dystrophies  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and limb girdle muscular dystrophies (LGMD) represent a significant proportion of paediatric and adult neuromuscular neurology practice. The proactive symptom-based multidisciplinary team (MDT) management and access to non-invasive ventilation have enabled improved survival into adulthood. Nevertheless the severe disability imposed by conditions such as DMD poses a challenge for successful transition of

A Y Manzur; F Muntoni

2009-01-01

63

Disease taxonomy - monogenic muscular dystrophy  

Microsoft Academic Search

The field of the autosomal recessive progressive muscular dystrophies has clarified significantly following the recent elucidation of the genetic and molecular etiology of a number of these entities. These studies illustrate how genetics provides a rationale and objective basis for a new, refined nosology. Furthermore, whereas most of these studies point towards the pivotal role played by a number of

Jacques S Beckmann

1999-01-01

64

Cardiomyopathy of Duchenne muscular dystrophy  

Microsoft Academic Search

Summary A total of 18 male patients with Duchenne muscular dystrophy (DMD), aged 8–29 years (mean, 15.7 years), were prospectively studied to assess the cardiomyopathy associated with DMD, using clinical parameters and noninvasive cardiovascular investigations: electrocardiogram (ECG), Holter monitoring, and echocardiography. In addition, five clinical tests of cardiovascular autonomic function were used to assess the role of the autonomic nervous

Luigi D'Orsogna; John P. O'Shea; Geoffrey Miller

1988-01-01

65

[Respiratory management in muscular dystrophies].  

PubMed

Respiratory failure is a major contributor to immobility and mortality in progressive muscular dystrophies. The severity of pulmonary impairment and the stage at which it develops differ according to the type of muscular dystrophy. Appropriate respiratory management for each type should be considered. In Duchenne muscular dystrophy (DMD), respiratory impairment manifests in the late teens, and assisted mechanical ventilation is administered. Noninvasive positive-pressure ventilation (NIPPV) has increased the median survival of patients with DMD by 10 year and improved quality of life. In myotonic dystrophy (MyD), the causes of respiratory failure can involve both the central and the peripheral nervous systems in addition to respiratory muscles. Nocturnal desaturation is more severe in MyD than in other muscular dystrophies with similar degrees of respiratory muscle weakness. Cognitive impairment should be taken into account in the management of MyD patients. NIPPV does not appear to improve survival of MyD. Guidelines for DMD have been published. Respiratory function should be assessed serially by measuring forced vital capacity, oxyhemoglobin saturation, peak cough flow, and end-tidal CO2 level. A respiratory action plan should be enacted with increasing disease severity. Therapeutic measures comprise airway clearance, respiratory muscle training, noninvasive nocturnal ventilation, daytime noninvasive ventilation, and continuous invasive ventilation. At the advanced stage of respiratory failure, attention should be paid to complications related to long-term mechanical ventilation, such as pneumothorax and tracheal hemorrhage. Discussing about end-of-life care among the patient, family, and physician is important before mechanical ventilatory support is required. PMID:22068475

Kuru, Satoshi

2011-11-01

66

Linkage Analyses in Tibial Muscular Dystrophy  

Microsoft Academic Search

Tibial muscular dystrophy (TMD) is a recently described muscular disease first discovered in a highly consanguineous family in Finland. The pedigree also included patients whose symptoms resembled another phenotype, classical limb-girdle muscular dystrophy. Extensive linkage analysis was carried out in this complex pedigree using 157 highly polymorphic DNA markers. Because of the presence of two phenotypes, several inheritance models were

P. Nokelainen; B. Udd; H. Somer; L. Peltonen

1996-01-01

67

Therapeutics in Duchenne muscular dystrophy  

Microsoft Academic Search

Summary  Duchenne muscular dystrophy (DMD) is a fatal disorder affecting approximately 1 in 3500 live born males, characterized by\\u000a progressive muscle weakness. Several different strategies are being investigated in developing a cure for this disorder. Until\\u000a a cure is found, therapeutic and supportive care is essential in preventing complications and improving the afflicted child’s\\u000a quality of life. Currently, corticosteroids are the

Jonathan B. Strober

2006-01-01

68

Defective Glycosylation and Muscular Dystrophies  

Microsoft Academic Search

A number of forms of congenital muscular dystrophy (CMD) have now been identified that involve defects in the glycosylation\\u000a of dystroglycan with O-mannosyl-linked glycans. Unlike many neurologic disorders, altered glycosylation in CMDs does not cause\\u000a aberrant protein aggregation or loss of expression. Instead, defects in glycosylation inhibit the binding of extracellular\\u000a matrix proteins such as laminin to dystroglycan on neuronal

Paul T. Martin

69

Expression profiling of muscles from Fukuyama-type congenital muscular dystrophy and laminin-?2 deficient congenital muscular dystrophy; is congenital muscular dystrophy a primary fibrotic disease?  

Microsoft Academic Search

Fukuyama-type congenital muscular dystrophy (FCMD) and laminin-?2 deficient congenital muscular dystrophy (MDC1A) are congenital muscular dystrophies (CMDs) and they both are categorized into the same clinical entity of muscular dystrophy as Duchenne muscular dystrophy (DMD). All three disorders share a common etiologic defect in the dystrophin–glycoprotein complex, which connects muscle structural proteins with the extracellular basement membrane. To investigate the

Mariko Taniguchi; Hiroki Kurahashi; Satoru Noguchi; Jun Sese; Takeshi Okinaga; Toshifumi Tsukahara; Pascale Guicheney; Keiichi Ozono; Ichizo Nishino; Shinichi Morishita; Tatsushi Toda

2006-01-01

70

Ullrich's congenital atonic sclerotic muscular dystrophy  

Microsoft Academic Search

A 5-year old girl with Ullrich's atonic-sclerotic muscular dystrophy is reported and 16 previously reported cases are reviewed. The clinical features, in particular proximal contractures, distal hyperextensibility, mild dysmorphism and hyperhidrosis, allow recognition of this subtype of congenital muscular dystrophy, which has no specific pathological characteristics. There is evidence in favour of an autosomal recessive mode of inheritance.

L. De Paillette; J. Aicardi; F. Goutières

1989-01-01

71

Coexisting Muscular Dystrophies and Epilepsy in Children  

Microsoft Academic Search

Muscular dystrophies are composed of a variety of genetic muscle disorders linked to different chromosomes and loci and associated with different gene mutations that lead to progressive muscle atrophy and weakness. Fukuyama congenital muscular dystrophy is frequently associated with partial and generalized epilepsy and congenital brain anomalies, including cobblestone complex and other neuronal migration defects. We report generalized convulsive epilepsy

Chang-Yong Tsao; J. R. Mendel

2006-01-01

72

Congenital Muscular Dystrophy in Arab Children  

Microsoft Academic Search

The congenital muscular dystrophies are autosomal recessive disorders with different clinical phenotypes, the spectrum of which varies between different ethnic communities. We report our findings in 21 Arab children with congenital muscular dystrophy. All 21 cases were of the pure type, with normal mental status, except 1 case with perinatal hypoxic-ischemic insult. Fourteen were laminin ?2 (merosin) deficient, and six

Yousif K. R. Habeeb; Maliha A. Al-Bloushi; Eman S. Al-Jumah; Thomas M. De Souza; Allie Moosa

2006-01-01

73

Rehabilitation of the muscular dystrophies.  

PubMed

The muscular dystrophies (MD) are a heterogeneous group of inherited disorders characterized by findings on muscle biopsy. In general, they feature progressive muscle wasting and weakness. In addition to the musculoskeletal system, direct and indirect effects can be seen in a variety of organ systems. These issues create challenges in patients with MD for ambulation and mobility, self-care, pain, fatigue, and community involvement. Because of its progressive nature and wide variety of pathophysiological mechanisms, patients with MD require individualized rehabilitation care. This chapter reviews specific rehabilitation needs and treatment of patients with MD. PMID:23312665

Pangilinan, Percival H; Hornyak, Joseph E

2013-01-01

74

Acquired noncompaction in Duchenne muscular dystrophy  

Microsoft Academic Search

Acquired left ventricular hypertrabeculation\\/noncompaction (LVHT) is rare and has been described in patients with mitochondriopathy, Barth syndrome, and Becker muscular dystrophy. Here we report acquired LVHT in a 28-year-old man with Duchenne muscular dystrophy who required non-invasive, positive-pressure ventilation for muscular respiratory failure since age 16 years. Transthoracic echocardiography at age 22 years revealed enlarged left atrium and ventricle and

Josef Finsterer; Claudia Stöllberger; Kurt Gaismayer; Bart Janssen

2006-01-01

75

Zebrafish orthologs of human muscular dystrophy genes  

PubMed Central

Background Human muscular dystrophies are a heterogeneous group of genetic disorders which cause decreased muscle strength and often result in premature death. There is no known cure for muscular dystrophy, nor have all causative genes been identified. Recent work in the small vertebrate zebrafish Danio rerio suggests that mutation or misregulation of zebrafish dystrophy orthologs can also cause muscular degeneration phenotypes in fish. To aid in the identification of new causative genes, this study identifies and maps zebrafish orthologs for all known human muscular dystrophy genes. Results Zebrafish sequence databases were queried for transcripts orthologous to human dystrophy-causing genes, identifying transcripts for 28 out of 29 genes of interest. In addition, the genomic locations of all 29 genes have been found, allowing rapid candidate gene discovery during genetic mapping of zebrafish dystrophy mutants. 19 genes show conservation of syntenic relationships with humans and at least two genes appear to be duplicated in zebrafish. Significant sequence coverage on one or more BAC clone(s) was also identified for 24 of the genes to provide better local sequence information and easy updating of genomic locations as the zebrafish genome assembly continues to evolve. Conclusion This resource supports zebrafish as a dystrophy model, suggesting maintenance of all known dystrophy-associated genes in the zebrafish genome. Coupled with the ability to conduct genetic screens and small molecule screens, zebrafish are thus an attractive model organism for isolating new dystrophy-causing genes/pathways and for use in high-throughput therapeutic discovery.

Steffen, Leta S; Guyon, Jeffrey R; Vogel, Emily D; Beltre, Rosanna; Pusack, Timothy J; Zhou, Yi; Zon, Leonard I; Kunkel, Louis M

2007-01-01

76

Partial Epilepsy in an Adolescent Male With Limb-Girdle Muscular Dystrophy 1B  

Microsoft Academic Search

Muscular dystrophies are inherited muscle disorders associated with different gene mutations. Fukuyama congenital muscular dystrophy is associated with cobblestone lissencephaly and epilepsy frequently. Rarely, other types of muscular dystrophies are also associated with epilepsy including Duchenne and Becker muscular dystrophy, facioscapulohumeral dystrophy, congenital muscular dystrophy with partial and complete deficiency of laminin ?2 chain, and limb-girdle muscular dystrophy 2A with

Chang-Yong Tsao; Jerry R. Mendell

2009-01-01

77

Genetics Home Reference: Oculopharyngeal muscular dystrophy  

MedlinePLUS

... contains an area where the protein building block (amino acid) alanine is repeated 10 times. This stretch ... glossary definitions help with understanding oculopharyngeal muscular dystrophy? amino acid ; atrophy ; autosomal ; autosomal dominant ; autosomal recessive ; cell ; ...

78

Subclinical cardiomyopathy in Becker muscular dystrophy  

Microsoft Academic Search

Objective—To investigate the prevalence, age distribution, and spectrum of cardiac involvement in a cohort of patients with Becker muscular dystrophy.Design—A prospective non-invasive study with clinical, electrocardiographic, and echocardiographic assessment.Patients—19 patients (age range 16–41 years) with Becker muscular dystrophy attending the Muscle Clinic at Hammersmith Hospital and 22 healthy controls (age range 22–36 years).Results—17 patients (89%) were symptom free; two had

Stephen E Steare; Victor Dubowitz; Avram Benatar

1992-01-01

79

Cerebral infarction in Duchenne muscular dystrophy.  

PubMed

Duchenne muscular dystrophy (DMD) is an X-linked form of muscular dystrophy characterized by progressive limb-girdle distribution of muscle weakness. Morbidity related to cardiomyopathy (CMO) is common, but cerebral infarction (CI) is relatively rare in these patients. We report a case of a pontine infarct in a patient with DMD and advanced CMO, and review the published data on CMO and CI in patients with DMD. PMID:20621521

Tsakadze, Nina; Katzin, Lara W; Krishnan, Sendhil; Behrouz, Réza

2010-07-10

80

Obstructive apnoeas in Duchenne muscular dystrophy  

Microsoft Academic Search

BACKGROUND--In order to clarify the treatment of sleep hypoxaemias in Duchenne muscular dystrophy polysomnographic studies were performed on patients at home with the purpose of recruiting them into two clinical therapeutic trials. Observations concerning the nature of sleep hypoxaemia in these patients are presented. METHODS--Twenty one non-ambulant patients with Duchenne muscular dystrophy aged 13-23 years with no symptoms of sleep

Y Khan; J Z Heckmatt

1994-01-01

81

Facioscapulohumeral muscular dystrophy assessment and treatment  

Microsoft Academic Search

Facioscapulohumeral dystrophy (FSHD), is a muscular dystrophy that classically affects the shoulder girdle and facial muscles. It should be considered in the differential diagnosis of patients presenting with limb girdle weakness. Progression is usually slow, and the condition is rarely fatal. Treatment is mostly supportive, although a number of patients can be helped with scapulo-thoracic fusion. This paper summarises the

Samuel J. Parsons; Andrew McMurtrie; Stephen Cooke; Birender Balain; David Jaffray

2009-01-01

82

Type III spinal muscular atrophy mimicking muscular dystrophies.  

PubMed

Types III and IV spinal muscular atrophy represent a diagnostic challenge due to the great variability in their presentation. We report a series of eight patients with type III spinal muscular atrophy who were followed for a long time for possible muscular dystrophy or myopathy, confirming its clinical heterogeneity and propensity to delayed diagnosis. Clinical examination revealed heterogeneous findings, where the diagnosis of type III spinal muscular atrophy was not immediately apparent in many patients as their clinical and laboratory abnormalities were consistent with muscular dystrophy or myopathy. The presence of dystrophic features such as hypertrophy of the calves, weakness of the limb girdle, high serum creatine kinase levels, and myopathic histopathology should not divert attention from the possibility of spinal muscular atrophy. It is strongly recommended to give variable presentations enough thought and to consider the autosomal recessive type III spinal muscular atrophy in the diagnostic evaluation. PMID:23583053

Alsaman, Abdulaziz S; Alshaikh, Nahla M

2013-05-01

83

[Soluble adhesion molecules in muscular dystrophy].  

PubMed

To determine whether soluble adhesion molecules are affected in muscular dystrophy, we measured serum levels of creatine kinase (CK), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble (s) E-selectin, and fibrin and fibrinogen degradation products (FDP) in 25 patients with Duchenne muscular dystrophy (DMD), 7 with Becker muscular dystrophy, 7 with Fukuyama type congenital muscular dystrophy, 6 with myotonic dystrophy (MyD), and 5 with spinal muscular atrophy (SMA) type 2, and also serum sVCAM-1, sICAM-1, and sE-selectin in 9 healthy controls. The levels of sVCAM-1 in the patients with DMD were 367.0-852.0 ng/ml (552.8 +/- 23.1) and significantly elevated than those in the patients with MyD, SMA type 2, and controls. The levels of sICAM-1 and sE-selectin in the patients with muscular dystrophy were 0.2-376.0 ng/ml and 17.9-119.0 ng/ml, respectively. They were also elevated than those in the patients with SMA type 2 and controls, but not significantly. The levels of sVCAM-1 and sE-selectin in the patients with DMD significantly correlated with age. There was no correlation between the levels of soluble adhesion molecules and those of CK or FDP in any groups. These changes of soluble adhesion molecules may reflect the process of muscle destruction and endothelial cell activation in muscular dystrophy. PMID:12134684

Saito, Toshio; Yamamoto, Yuko; Shinno, Susumu

2002-07-01

84

Merosin and congenital muscular dystrophy.  

PubMed

Merosin (also called as Laminin-2) is an isoform of laminin comprised of the alpha2, beta1 and gamma1 chains. In European populations, half of the patients with classical congenital muscular dystrophy have mutations of the LAMA2 gene (6q22-23) and present reduced or absence of laminin alpha2 chain. This form is generally referred to as merosin-deficient CMD. Merosin-deficient CMD is characterized by involvement of not only skeletal muscle but also central and peripheral nervous systems: Extensive brain white matter abnormalities are found by magnetic resonance imaging (MRI). However, most patients show no mental retardation. Recent case studies reported that some patients have several structural abnormalities such as abnormal cerebral cortical gyration, hypoplasia of cerebellum and pons, and dilation of ventricles. At present, functions of merosin related to muscle degeneration have not been fully elucidated. In addition, the mechanisms responsible for pathogenesis of diffuse brain white matter abnormalities remain to be determined. As mouse models for merosin-deficient CMD, three spontaneous mutants(dy, dy(2J), dy(PAS1)) and two mutants named dy(W) and dy(3K) by targeted gene disruption have been reported. These mice will help to elucidate the pathogenesis of merosin-deficient CMD and serve to develop therapy. PMID:10679965

Miyagoe-Suzuki, Y; Nakagawa, M; Takeda, S

85

Autosomal-dominant dystrophy with humeroperoneal weakness and cardiopathy: a genetic variant of Emery-Dreifuss disease?  

Microsoft Academic Search

Two females mother and daughter, were affected by a neuromuscular disorder, characterized by slow progression, humeroperoneal weakness and wasting, limited neck flexion, elbow and ankle joint contractures, cardiopathy and myopathic pattern on EMG. Muscle histology and histochemistry showed type I fiber atrophy and predominance in both. Cardiac abnormalities, in the first case, were suggestive of a hypertrophic cardiomyopathy while in

G. Galassi; M. G. Modena; A. Benassi; R. Nemni; M. Gibertoni; G. Volpi; A. Colombo

1986-01-01

86

Simulation and analysis of needle electromyogram in Emery-Dreifuss Muscular Distrophy by using line source model  

Microsoft Academic Search

Electromyography (EMG) is a valuable clinical test in detection of muscle and nerve pathology and distinguishing between myogenic and neurogenic conditions from normal condition. By using EMG, one assesses the pathophysiology on the basis of the waveform characteristics of the recorded signal. This requires detailed knowledge of the relationship between the waveform generators and the waveform measurements. In this study,

H. Zivari Adab; S. M. P. Firoozabadi; S. Chalavi; K. Maghooli

2008-01-01

87

Consensus Statement on Standard of Care for Congenital Muscular Dystrophies  

Microsoft Academic Search

Congenital muscular dystrophies are a group of rare neuromuscular disorders with a wide spectrum of clinical phenotypes. Recent advances in understanding the molecular pathogenesis of congenital muscular dystrophy have enabled better diagnosis. However, medical care for patients with congenital muscular dystrophy remains very diverse. Advances in many areas of medical technology have not been adopted in clinical practice. The International

Ching H. Wang; Carsten G. Bonnemann; Anne Rutkowski; Thomas Sejersen; Jonathan Bellini; Vanessa Battista; Julaine M. Florence; Ulrike Schara; Pamela M. Schuler; Karim Wahbi; Annie Aloysius; Robert O. Bash; Christophe Béroud; Enrico Bertini; Kate Bushby; Ronald D. Cohn; Anne M. Connolly; Nicolas Deconinck; Isabelle Desguerre; Michelle Eagle; Brigitte Estournet-Mathiaud; Ana Ferreiro; Albert Fujak; Nathalie Goemans; Susan T. Iannaccone; Patricia Jouinot; Marion Main; Paola Melacini; Wolfgang Mueller-Felber; Francesco Muntoni; Leslie L. Nelson; Jes Rahbek; Susana Quijano-Roy; Caroline Sewry; Kari Storhaug; Anita Simonds; Brian Tseng; Jiri Vajsar; Andrea Vianello; Reinhard Zeller

2010-01-01

88

Airway nitric oxide in Duchenne muscular dystrophy.  

PubMed

The expression of muscle membrane-associated neuronal nitric oxide synthase (NOS1) is significantly impaired in Duchenne muscular dystrophy. Mean (+/- SEM) exhaled NO in 13 male patients with Duchenne muscular dystrophy was significantly lower than in 11 healthy age-matched male control subjects (7.5 +/- 1.4 vs 16.6 +/- 3.2 parts per billion, P <.02) or 17 adult male control subjects (18.5 +/- 1.8 parts per billion, P <.001). These findings provide indirect evidence that NOS1 contributes significantly to fractional exhaled nitric oxide in healthy children. PMID:12091865

Straub, Volker; Ratjen, Felix; Amthor, Helge; Voit, Thomas; Grasemann, Hartmut

2002-07-01

89

Cardiopulmonary Support in Duchenne Muscular Dystrophy  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD) is an X-linked, rapidly progressive myopathy affecting the limb muscles, the respiratory\\u000a muscles, the heart, the intestines, and the brain. Since about 90% of DMD patients die from muscular respiratory failure or\\u000a cardiomyopathy, early and adequate therapy is essential. Ventilatory failure from muscle weakness requires mechanical support\\u000a for ventilation and coughing as soon as there is

Josef Finsterer

2006-01-01

90

Visuospatial Attention Disturbance in Duchenne Muscular Dystrophy  

ERIC Educational Resources Information Center

|Aim: The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to…

De Moura, Maria Clara Drummond Soares; do Valle, Luiz Eduardo Ribeiro; Resende, Maria Bernadete Dutra; Pinto, Katia Osternack

2010-01-01

91

Advances in Duchenne muscular dystrophy gene therapy  

Microsoft Academic Search

Since the initial characterization of the genetic defect for Duchenne muscular dystrophy, much effort has been expended in attempts to develop a therapy for this devastating childhood disease. Gene therapy was the obvious answer but, initially, the dystrophin gene and its product seemed too large and complex for this approach. However, our increasing knowledge of the organization of the gene

Gert-Jan B. van Ommen; Judith C. T. van Deutekom

2003-01-01

92

Role of Apoptosis in Duchenne's Muscular Dystrophy  

Microsoft Academic Search

We investigated the presence of apoptosis in muscle tissues from 24 patients (average age 5.44 ± 1.81 years) with Duchenne's muscular dystrophy by in situ tailing of nuclear fragmentation. Muscle tissue from 4 children without histologic evidence of myopathy served as normal controls. Muscle fibers positive for nuclear DNA fragmentation were determined quantitatively by counting an area of at least

Ayse Serdaroglu; Kivilcim Gücüyener; Sevim Erdem; Gül?en Köse; Ersin Tan; Çetin Okuyaz

2002-01-01

93

Congenital Muscular Dystrophy in Israeli Families  

Microsoft Academic Search

Twelve patients from 11 Israeli families with congenital muscular dystrophy were evaluated between 1991 and 2001. There were six males and six females, of whom six were merosin negative and six were merosin positive. Serum creatine kinase levels were highly elevated in the merosin-negative group. Four of the children were cognitively normal but nonambulant. Two had unusual clinical findings of

Marianna Rachmiel; Yoram Nevo; Eli Lahat; Miriam Kutai; Shaul Harel; Eli Shahar

2002-01-01

94

Sporadic cases in Duchenne muscular dystrophy  

Microsoft Academic Search

A new estimation of the proportion of sporadic cases in Duchenne muscular dystrophy was attempted by means of segregation analysis in a sample of 988 sibships collected on a world-wide scale by different authors. Maximum likelihood estimates of ascertainment probability (p), segregation frequency (p), and frequency of sporadic cases (x) were calculated by Morton's equations under different hypotheses. The best

Antonella Russo; Guido Barbujani I; Maria Luisa Mostacciuolo; Falko H. Herrmann; Aribert W. J. Spiegler; Giuliana Galluzzi; Gian Antonio Danieli

1987-01-01

95

Severe phenotype in infantile facioscapulohumeral muscular dystrophy  

Microsoft Academic Search

While much is known about the clinical course of adult FSHD, the third most common inherited muscular dystrophy, data on the “infantile phenotype” and especially on the progression of the disease in children are limited. We have followed a cohort of 7 patients with infantile FSHD for 9–25 years and here report the clinical and genetic findings in this group.

Lars Klinge; Michelle Eagle; Irene D. Haggerty; Catherine E. Roberts; Volker Straub; Kate M. Bushby

2006-01-01

96

White matter abnormalities in congenital muscular dystrophy  

Microsoft Academic Search

Central nervous system (CNS) characteristics were examined in seventeen patients with autosomal recessive classic or “pure” congenital muscular dystrophy (CMD). In three patients, neuroradiological examination (CT\\/MRI) indicated hypodense white matter areas. Two out of these three patients had epilepsy (seizures and epileptic discharges on their EEG). Only two of the remaining patients had epileptic EEG discharges, but without clinical seizures.

Q. H. Leyten; F. J. M. Gabreëls; W. O. Renier; B. G. M. van Engelen; H. J. ter Laak; R. C. A. Sengers; H. O. M. Thijssen

1995-01-01

97

Muscular dystrophies: diagnostic approaches in Hungary.  

PubMed

Muscular dystrophies are a genetically heterogeneous group of degenerative muscle disorders. This article focuses on two severe forms of muscular dystrophies and provides genetic data for a large cohort of Hungarian patients diagnosed within the last few years by the authors. The Duchenne/Becker muscular dystrophy (DMD/BMD) is caused by mutations in the dystrophin gene, which is located on chromosome Xp21. The genetic analysis of dystrophin is usually performed by multiplex polymerase chain reaction (PCR), which detects approximately 95% of all deletions but does not distinguish between one and two copies of the exons investigated. The present work, therefore, concentrates on the improvement of the diagnostic panel for the analysis of DMD/BMD in Hungary. Radioactively labelled cDNA probes, encompassing the whole dystrophin gene detect all the deletions and the analysis is quantitative. In addition, the new multiple ligation-dependent probe amplification (MLPA) technique was recently introduced that enabled more reliable and faster quantitative detection of the entire dystrophin gene. The genomic basis of facioscapulohumeral muscular dystrophy (FSHD) is associated with contraction of the D4Z4 repeat region in the subtelomere of chromosome 4q. In case of FSHD, molecular genetic criteria still have to be improved because of the complexity of the disorder. PMID:19009915

Pikó, H; Vancsó, V; Nagy, B; Balog, J; Nagymihály, M; Herczegfalvi, A; Tímár, L; Bán, Z; Karcagi, V

2008-12-01

98

Lung function in Duchenne muscular dystrophy  

Microsoft Academic Search

Over 90% of patients with Duchenne muscular dystrophy develop a scoliosis when they become wheelchair bound. The scoliosis is progressive and is associated with deteriorating lung function. The purpose of this study was firstly to assess whether a standing regimen, in patients who had gone off their feet, protected against the development of scoliosis and affected their lung function, and

C. S. B. Galasko; J. B. Williamson; C. M. Delaney

1995-01-01

99

Deflazacort treatment of Duchenne muscular dystrophy  

Microsoft Academic Search

Objective: We report the long-term effects on muscle strength and side effects with deflazacort in Duchenne muscular dystrophy (DMD). Study design: Boys with DMD between the ages of 7 and 15 years were reviewed retrospectively; 30 had been treated with deflazacort, and 24 had not. Muscle function, pulmonary function, and side effects were compared. Results: The boys not treated with

W. Douglas Biggar; Michele Gingras; Darcy L. Fehlings; Vivien A. Harris; Catherine A. Steele

2001-01-01

100

Brain function in Duchenne muscular dystrophy  

Microsoft Academic Search

Summary Duchenne muscular dystrophy (DMD) is the second most commonly occurring genetically inherited disease in humans. It is an X-linked condition that affects approximately one in 3300 live male births. It is caused by the absence or disruption of the protein dystrophin, which is found in a variety of tissues, most notably skel- etal muscle and neurones in particular regions

J. L. Anderson; C. Rae; J. W. Morley

2002-01-01

101

Infantile autism and Duchenne muscular dystrophy  

Microsoft Academic Search

We report a boy with autism and Duchenne muscular dystrophy. Myopathy was noted after 2 years of age and has since progressed\\u000a slowly. At present this autistic child, 11 years 4 months old, has shown no signs of deterioration.

Junko Komotofl; Seigo Usui; Saburo Otsuki; Akira Terao

1984-01-01

102

Germinal mosaicism in Duchenne muscular dystrophy  

Microsoft Academic Search

We have identified a Duchenne muscular dystrophy (DMD) pedigree where the disease is associated with a molecular deletion within the DMD locus. We have examined the meiotic segregation products of the common female ancestor using marker restriction fragment length polymorphisms (RFLPs) detected by probes that lie within this deletion. These studies show that this female has transmitted three distinet types

Stephen Wood; Barbara C. McGillivray

1988-01-01

103

Modifying muscular dystrophy through transforming growth factor-?.  

PubMed

Muscular dystrophy arises from ongoing muscle degeneration and insufficient regeneration. This imbalance leads to loss of muscle, with replacement by scar or fibrotic tissue, resulting in muscle weakness and, eventually, loss of muscle function. Human muscular dystrophy is characterized by a wide range of disease severity, even when the same genetic mutation is present. This variability implies that other factors, both genetic and environmental, modify the disease outcome. There has been an ongoing effort to define the genetic and molecular bases that influence muscular dystrophy onset and progression. Modifier genes for muscle disease have been identified through both candidate gene approaches and genome-wide surveys. Multiple lines of experimental evidence have now converged on the transforming growth factor-? (TGF-?) pathway as a modifier for muscular dystrophy. TGF-? signaling is upregulated in dystrophic muscle as a result of a destabilized plasma membrane and/or an altered extracellular matrix. Given the important biological role of the TGF-? pathway, and its role beyond muscle homeostasis, we review modifier genes that alter the TGF-? pathway and approaches to modulate TGF-? activity to ameliorate muscle disease. PMID:23551962

Ceco, Ermelinda; McNally, Elizabeth M

2013-04-24

104

CURRICULUM VITAE  

Center for Biologics Evaluation and Research (CBER)

Text Version... at P183 of emerin weaken its protein-protein interactions resulting in X-linked Emery-Dreifuss muscular dystrophy", Human Genetics, 104(3): 262 ... More results from www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials

105

Oculopharyngeal Muscular Dystrophy in an Irish Family  

Microsoft Academic Search

Summary  Victor1 and his associates coined the term oculopharyngeal muscular dystrophy to describe a clinical syndrome characterised by dysphagia\\u000a and ptosis. Subsequent authors have traced a large series in French Canadians to a single Quebec isolate and have emphasized\\u000a that the condition is usually inherited as a dominant trait2,3. In 1974 Fried4 reported two isolated cases in an Ashkenazi Jewish family

S. Eustace; C. Gleeson; M. Joyce; P. Sullivan

1989-01-01

106

Cardiac Involvement in Facioscapulohumeral Muscular Dystrophy  

Microsoft Academic Search

Cardiac involvement (CI) in form of myocardial thickening in a patient with genetically confirmed facioscapulohumeral muscular dystrophy (FSHMD) has not been reported. The patient is a 50-year-old male with a tandem repeat size of 17 and 14 kb in the D4Z4 locus on chromosome 4q35. The clinical cardiologic investigation was normal. Blood pressure was 150\\/90 mm Hg. Funduscopy, 24-hour ambulatory

Josef Finsterer; Claudia Stöllberger; Gerhard Meng

2005-01-01

107

Congenital Muscular Dystrophies: Toward Molecular Therapeutic Interventions  

Microsoft Academic Search

Congenital muscular dystrophies (CMDs) are a clinically and genetically heterogeneous group of neuromuscular disorders that\\u000a typically present at birth or in early infancy with hypotonia, weakness, and histologic evidence of a dystrophic myopathy.\\u000a CMD biochemical types include various abnormalities of ?-dystroglycan O-mannosyl glycosylation as well as defects in integrin matrix receptors, the extracellular matrix proteins laminin-?2 and collagen VI, nuclear

James Collins; Carsten G. Bönnemann

2010-01-01

108

Plasma thyroxine levels in Duchenne muscular dystrophy  

Microsoft Academic Search

Summary Some young Duchenne muscular dystrophy (DMD) patients (3–7 years) had total thyroxine (T4) levels and T4 to thyroxine binding globulin (TBG) ratios above the normal range and significantly increased free thyroxine indices (fT4I) which, however, remained within the normal range. Older DMD patients (7–11 years) had T4 and TBG levels and fT4I similar to normal. In both DMD groups

H. A. John

1990-01-01

109

Germline mosaicism and Duchenne muscular dystrophy mutations  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disease with an incidence of ~1 in 3,500 newborn boys. The DMD locus has a high mutation frequency: one third of the cases is thought to result from a new mutation1. Linkage studies using probes to detect restriction fragment length polymorphisms2 and DNA deletion studies3 have greatly improved DMD carrier detection

E. Bakker; Ch. Van Broeckhoven; E. J. Bonten; M. J. van de Vooren; H. Veenema; W. Van Hul; G. J. B. Van Ommen; A. Vandenberghe; P. L. Pearson

1987-01-01

110

Clinical features of facioscapulohumeral muscular dystrophy 2  

Microsoft Academic Search

OBJECTIVE: In some 5% of patients with facioscapulohumeral muscular dystrophy (FSHD), no D4Z4 repeat contraction on chromosome 4q35 is observed. Such patients, termed patients with FSHD2, show loss of DNA methylation and heterochromatin markers at the D4Z4 repeat that are similar to patients with D4Z4 contractions (FSHD1). This commonality suggests that a change in D4Z4 chromatin structure unifies FSHD1 and

J. C. de Greef; R. J. Lemmers; P. Camano; J. W. Day; S. Sacconi; M. Dunand; B. G. M. van Engelen; S. Kiuru-Enari; G. W. A. M. Padberg; A. L. Rosa; C. Desnuelle; S. Spuler; M. Tarnopolsky; S. L. Venance; R. R. Frants; S. M. van der Maarel; R. Tawil

2010-01-01

111

Cardiac Assessment in Duchenne and Becker Muscular Dystrophies  

Microsoft Academic Search

Mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophies. In addition to muscle disease, there nearly\\u000a always is an associated cardiomyopathy in Duchenne or Becker muscular dystrophy. In these muscular dystrophies, the severity\\u000a of cardiomyopathy and congestive heart failure may not parallel the severity of skeletal muscle disease. Loss of normal dystrophin\\u000a function in the heart produces four-chamber

Anitra Romfh; Elizabeth M. McNally

2010-01-01

112

[Myocardiopathy of progressive muscular dystrophy].  

PubMed

The authors have effected a clinical, radiological, electrocardiographic and apexocardiographic survey in 13 patients with progressive muscular distrophy (PMD) and in 6 healthy subjects belonging to families affected by the disease, in parallel with a group of 11 patients with severe myasthenia and 23 healthy subjects. Comparing the results with those found in the literature lead to the following results: 1) The ECG modifications and above all the abnormalities of the ventricular complex develop precociously in the PMD and express the pleiotropism of the myopathic gene. 2) The myocardial dyssynergia represents a link in the physiopathological chain of the cardiac distress. 3) The precociousness of electro and apexocardiographic modifications and their presence in healthy parents recommend these investigations in the genetic enquiry. 4) Clinical, histological and haemodynamic data individualize the myocardial distress as a true myocardiopathy. PMID:1005267

Ion, I C; Dumitriu, M; Nisipeanu, P; Cinteza, M

1976-01-01

113

Limb-girdle muscular dystrophy in Guipuzcoa (Basque Country, Spain)  

Microsoft Academic Search

Summary The concept of limb-girdle muscular dystrophy (LGMD) is changing rapidly due to the advances in molecular genetics. Recently, seven different gene loci have been described, demonstrating that limb-girdle muscular dystrophy is a heterogeneous syndrome, which includes different diseases with a similar phenotype. In isolated populations which have little genetic exchange with neighbouring populations, an accumulation of cases may be

M. Urtasun; A. Saenz; C. Roudaut; J. J. Poza; J. A. Urtizberea; A. M. Cobo; I. Richard; F. Garcia Bragado; F. Leturcq; J. C. Kaplan; J. F. MartiMasso; J. S. Beckmann; A. Lopez de Munain

1998-01-01

114

A New Probe for the Diagnosis of Myotonic Muscular Dystrophy  

Microsoft Academic Search

Myotonic muscular dystrophy (DM) is the most common muscular dystrophy, affecting adults as well as children. It is inherited as an autosomal dominant trait and is characterized by variable expressivity and late age-of-onset. Linkage studies have established the locus on chromosome 19. In order to identify tightly linked probes for diagnosis as well as to define in detail the DM

R. J. Bartlett; M. A. Pericak-Vance; L. Yamaoka; J. Gilbert; M. Herbstreith; W.-Y. Hung; J. E. Lee; T. Mohandas; G. Bruns; C. Laberge; M.-C. Thibault; D. Ross; A. D. Roses

1987-01-01

115

Rimmed vacuoles in facioscapulohumeral muscular dystrophy: a unique ultrastructural feature  

Microsoft Academic Search

Rimmed vacuoles (RV) are a characteristic pathological feature in inclusion body myositis, but may also occur in other neuromuscular disorders, such as distal myopathies, oculopharyngeal myopathy, polymyositis, rigid spine syndrome, congenital myopathies, and some limb girdle muscular dystrophies, as well as in various neurogenic diseases. We describe a patient with RV in familial facioscapulohumeral muscular dystrophy (FSHD) associated with an

Stephan Neudecker; Michael Krasnianski; Erik Bahn; Stephan Zierz

2004-01-01

116

Creatine kinase, cell membrane and Duchenne muscular dystrophy  

Microsoft Academic Search

In 1958 Professor Setsuro Ebashi found that serum creatine kinase activity is increased in patients suffering from various muscular dystrophies, especially Duchenne muscular dystrophy (DMD). He and others proposed that creatine kinase passes through the cell membrane as it is released from DMD muscle fibers.

Eijiro Ozawa; Yasuko Hagiwara; Mikiharu Yoshida

1999-01-01

117

Absence of hearing impairment in adult onset facioscapulohumeral muscular dystrophy  

Microsoft Academic Search

Hearing impairment has long been associated with the rarer forms of severe childhood and infantile facioscapulohumeral muscular dystrophy. Recent studies have suggested a high prevalence in classic, adult or adolescent, onset cases as well. We undertook detailed pure tone audiometric examination of 21 adult onset facioscapulohumeral muscular dystrophy cases. Patient results were compared with normative data obtained from the (United

Mark T Rogers; Fei Zhao; Peter S Harper; Dafydd Stephens

2002-01-01

118

DNA deletions in mild and severe Becker muscular dystrophy  

Microsoft Academic Search

The DNA of 33 patients diagnosed as suffering from Becker muscular dystrophy (BMD) has been probed with cloned DNA sequences from Xp21, known to reveal DNA deletions in patients suffering from the more severe Duchenne muscular dystrophy (DMD). Two BMD cases showed clear deletions. A third case gave aberrant band sizes, which further analysis showed to be caused by a

Kevin A. Hart; Shirley Hodgson; Alison Walker; Charlotte G. Cole; Lynn Johnson; Victor Dubowitz; Martin Bobrow I

1987-01-01

119

Cardiac Assessment in Duchenne and Becker Muscular Dystrophies  

Microsoft Academic Search

Background: Cardiac problems are common and are a major cause of death in both Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Early diagnosis and proper management are very important for prolonging life expectancy, improving mobility and the quality of life in dystrophinopathic patients. The object of this study was to assess the cardiac dysfunction in dystrophinopathic patients. Methods:

Tae-Jin Song; Young-Chul Choi

120

The neurobiology of Duchenne muscular dystrophy: learning lessons from muscle?  

Microsoft Academic Search

Several forms of inherited muscular dystrophy are associated with brain abnormalities and cognitive impairment. One of the most common and severe of these diseases is Duchenne muscular dystrophy (DMD). Dystrophin, the product of the DMD gene, is found in neurones, where it is associated with the postsynaptic membrane. Cognitive impairment in individuals with DMD is thought to be due to

Derek J. Blake; Stephan Kröger

2000-01-01

121

Defective membrane repair in dysferlin-deficient muscular dystrophy  

Microsoft Academic Search

Muscular dystrophy includes a diverse group of inherited muscle diseases characterized by wasting and weakness of skeletal muscle. Mutations in dysferlin are linked to two clinically distinct muscle diseases, limb-girdle muscular dystrophy type 2B and Miyoshi myopathy, but the mechanism that leads to muscle degeneration is unknown. Dysferlin is a homologue of the Caenorhabditis elegans fer-1 gene, which mediates vesicle

Dimple Bansal; Katsuya Miyake; Steven S. Vogel; Séverine Groh; Chien-Chang Chen; Roger Williamson; Paul L. McNeil; Kevin P. Campbell

2003-01-01

122

Therapeutic Targeting of Signaling Pathways in Muscular Dystrophy  

PubMed Central

Muscular dystrophy refers to a group of genetic diseases that cause severe muscle weakness and loss of skeletal muscle mass. Although research has helped understanding the molecular basis of muscular dystrophy, there is still no cure for this devastating disorder. Numerous lines of investigation suggest that the primary deficiency of specific proteins causes aberrant activation of several cell signaling pathways in skeletal and cardiac muscle leading to the pathogenesis of muscular dystrophy. Studies using genetic mouse models and pharmacological approaches have provided strong evidence that the modulation of the activity of specific cell signaling pathways has enormous potential to improving the quality of life and extending the life expectancy in muscular dystrophy patients. In this article, we have outlined the current understanding regarding the role of different cell signaling pathways in disease progression with particular reference to different models of muscular dystrophy and the development of therapy.

Bhatnagar, Shephali; Kumar, Ashok

2009-01-01

123

[Treatment progress of Duchenne Muscular Dystrophy (DMD)].  

PubMed

Duchenne muscular dystrophy (DMD) is a common lethal disease for which no effective treatment is currently available. There exists a mouse model of the disease in which the usefulness of gene therapy was established. However, no progress towards human application was made due to the lack of a proper method for gene delivery. During the past several years, researchers acquired data which led them to believe that bone marrow stem cells are capable of generating not only blood cells, but also liver, heart, skin, muscle, and other tissue. Although the term "stem cell plasticity" became very popular, other studies have suggested that bone marrow might contain different types of stem cells that can produce non-hematopoietic cells. For example, mesenchymal stem cell (MSC) in bone marrow give rise to osteocytes, chondrocytes, adipocytes, and skeletal muscle. Recently, researchers have been able to show that transplanted bone marrow cells can contribute to muscle cells in a human patient who was diagnosed with two genetic diseases: severe combined immunodeficiency (SCID) and Duchenne muscular dystrophy. The odds of this happening is estimated at one in seven million. The results of studying this patient's medical history were reported by collaborating researchers at Children's Hospital, Los Angeles and Children's Hospital, Boston in an article titled "Long-term persistence of donor nuclei in a Duchenne muscular dystrophy (DMD) patient receiving bone marrow transplantation" published in the September 2002 issue of the Journal of Clinical Investigation. This patient was transplanted 15 years ago at Children's Hospital Los Angeles with paternal HLA-haploidentical T cell-depleted bone marrow. He engrafted and became a hematopoietic chimera having T and NK lymphocytes of donor origin. Studies performed on the muscle biopsy from the patient 13 years after transplantation demonstrated that the muscle showed evidence of donor derived nuclei. In addition, analysis of his bone marrow showed that small numbers of MSC were also derived from the transplanted bone marrow. Unfortunately, there was no evidence that the number of new muscle cells from the donor was able to decrease the progression of his muscular dystrophy. The revelation of finding the donor's cells in the muscle of the patient provides new hope for patients with the same disease. In the future it may be possible for mesenchymal cells to be isolated, ex vivo expanded and transplanted into patients with muscle diseases. PMID:15557694

Smogorzewska, Elzbieta Monika; Weinberg, Kenneth I

124

Loss of Drosophila A-type lamin C initially causes tendon abnormality including disintegration of cytoskeleton and nuclear lamina in muscular defects.  

PubMed

Lamins are the major components of nuclear envelope architecture, being required for both the structural and informational roles of the nuclei. Mutations of lamins cause a spectrum of diseases in humans, including muscular dystrophy. We report here that the loss of the A-type lamin gene, lamin C in Drosophila resulted in pupal metamorphic lethality caused by tendon defects, matching the characteristics of human A-type lamin revealed by Emery-Dreifuss muscular dystrophy (EDMD). In tendon cells lacking lamin C activity, overall cell morphology was affected and organization of the spectraplakin family cytoskeletal protein Shortstop which is prominently expressed in tendon cells gradually disintegrated, notably around the nucleus and in a manner correlating well with the degradation of musculature. Furthermore, lamin C null mutants were efficiently rescued by restoring lamin C expression to shortstop-expressing cells, which include tendon cells but exclude skeletal muscle cells. Thus the critical function of A-type lamin C proteins in Drosophila musculature is to maintain proper function and morphology of tendon cells. PMID:22982669

Uchino, Ryo; Nonaka, Yu-Ki; Horigome, Tuneyoshi; Sugiyama, Shin; Furukawa, Kazuhiro

2012-09-13

125

Predicting hearing loss in facioscapulohumeral muscular dystrophy.  

PubMed

Facioscapulohumeral muscular dystrophy (FSHD) has an estimated prevalence of 4-7 per 100,000 population, making it the third most common type of muscular dystrophy. The classic form of FSHD is characterized by weakness that is slowly progressive and often asymmetric in the face, scapulae, upper arms, lower legs, and abdomen. The age at onset of symptoms varies from infancy to middle age, and life expectancy is normal or almost normal. Aside from muscle weakness, other manifestations include chronic pain, hearing loss, retinal telangiectasias and exudation (Coats syndrome) that can progress to retinal detachment and vision loss, cardiac arrhythmias, cognitive impairment, and epilepsy.(1) There seems to be an increased prevalence of hearing loss in FSHD compared with the general population. Hearing loss has been described particularly in patients with infantile-onset FSHD but also in typical cases.(2) In severe infantile-onset cases, the hearing loss can be profound, and if not detected may lead to delayed language development and even the false perception of cognitive impairment. Consensus-based recommendations suggest routine hearing testing in infants and preschool-age children diagnosed with FSHD.(3.) PMID:24042094

Darras, Basil T; Tawil, Rabi

2013-09-16

126

The superhealing MRL background improves muscular dystrophy  

PubMed Central

Background Mice from the MRL or “superhealing” strain have enhanced repair after acute injury to the skin, cornea, and heart. We now tested an admixture of the MRL genome and found that it altered the course of muscle pathology and cardiac function in a chronic disease model of skeletal and cardiac muscle. Mice lacking ?-sarcoglycan (Sgcg), a dystrophin-associated protein, develop muscular dystrophy and cardiomyopathy similar to their human counterparts with limb girdle muscular dystrophy. With disruption of the dystrophin complex, the muscle plasma membrane becomes leaky and muscles develop increased fibrosis. Methods MRL/MpJ mice were bred with Sgcg mice, and cardiac function was measured. Muscles were assessed for fibrosis and membrane leak using measurements of hydroxyproline and Evans blue dye. Quantitative trait locus mapping was conducted using single nucleotide polymorphisms distinct between the two parental strains. Results Introduction of the MRL genome reduced fibrosis but did not alter membrane leak in skeletal muscle of the Sgcg model. The MRL genome was also associated with improved cardiac function with reversal of depressed fractional shortening and the left ventricular ejection fraction. We conducted a genome-wide analysis of genetic modifiers and found that a region on chromosome 2 was associated with cardiac, diaphragm muscle and abdominal muscle fibrosis. Conclusions These data are consistent with a model where the MRL genome acts in a dominant manner to suppress fibrosis in this chronic disease setting of heart and muscle disease.

2012-01-01

127

Disease taxonomy--monogenic muscular dystrophy.  

PubMed

The field of the autosomal recessive progressive muscular dystrophies has clarified significantly following the recent elucidation of the genetic and molecular etiology of a number of these entities. These studies illustrate how genetics provides a rationale and objective basis for a new, refined nosology. Furthermore, whereas most of these studies point towards the pivotal role played by a number of structural proteins--all directly or indirectly associated with dystrophin--a calpain protease was shown to be involved in the Réunion-type limb girdle muscular dystrophy. This discovery raises the issue of whether these mechanisms are all part of one and the same pathway or of distinct pathophysiological pathways (structuropathy versus enzymopathy) leading to similar phenotypes. Finally, all of these diseases are considered as classical monogenic traits. Some findings suggest, however, that epistatic interactions have been overlooked and that the inheritance models could be slightly more complex. These results are discussed in light of the coming challenges of the identification of genes underlying complex multifactorial traits. PMID:10723861

Beckmann, J S

1999-01-01

128

Fractures of long bones in Duchenne muscular dystrophy.  

PubMed

The dangers of bed-confininf procedures in children with Duchenne Muscular Dystrophy should be recognized, and their fractures treated so as to encourage continued independent ambulation as long as feasible. PMID:850276

Siegel, I M

1977-03-01

129

uPA deficiency exacerbates muscular dystrophy in MDX mice  

PubMed Central

Duchenne muscular dystrophy (DMD) is a fatal and incurable muscle degenerative disorder. We identify a function of the protease urokinase plasminogen activator (uPA) in mdx mice, a mouse model of DMD. The expression of uPA is induced in mdx dystrophic muscle, and the genetic loss of uPA in mdx mice exacerbated muscle dystrophy and reduced muscular function. Bone marrow (BM) transplantation experiments revealed a critical function for BM-derived uPA in mdx muscle repair via three mechanisms: (1) by promoting the infiltration of BM-derived inflammatory cells; (2) by preventing the excessive deposition of fibrin; and (3) by promoting myoblast migration. Interestingly, genetic loss of the uPA receptor in mdx mice did not exacerbate muscular dystrophy in mdx mice, suggesting that uPA exerts its effects independently of its receptor. These findings underscore the importance of uPA in muscular dystrophy.

Suelves, Monica; Vidal, Berta; Serrano, Antonio L.; Tjwa, Marc; Roma, Josep; Lopez-Alemany, Roser; Luttun, Aernout; de Lagran, Maria Martinez; Diaz, Maria Angels; Jardi, Merce; Roig, Manuel; Dierssen, Mara; Dewerchin, Mieke; Carmeliet, Peter; Munoz-Canoves, Pura

2007-01-01

130

A new chart for weight control in Duchenne muscular dystrophy  

Microsoft Academic Search

Weight control is desirable in the muscle wasting conditions. A new chart is presented to allow the prediction of an ideal weight, free of excess fat, specifically for boys with Duchenne muscular dystrophy.

R D Griffiths; R H Edwards

1988-01-01

131

Experience with screening newborns for Duchenne muscular dystrophy in Wales  

Microsoft Academic Search

OBJECTIVES--To assess the acceptability of screening newborn boys for Duchenne muscular dystrophy. DESIGN--Screening is offered on the basis of informed consent in response to an information sheet entitled \\

D M Bradley; E P Parsons; A J Clarke

1993-01-01

132

Expression profiling of muscles from Fukuyama-type congenital muscular dystrophy and laminin-alpha 2 deficient congenital muscular dystrophy; is congenital muscular dystrophy a primary fibrotic disease?  

PubMed

Fukuyama-type congenital muscular dystrophy (FCMD) and laminin-alpha2 deficient congenital muscular dystrophy (MDC1A) are congenital muscular dystrophies (CMDs) and they both are categorized into the same clinical entity of muscular dystrophy as Duchenne muscular dystrophy (DMD). All three disorders share a common etiologic defect in the dystrophin-glycoprotein complex, which connects muscle structural proteins with the extracellular basement membrane. To investigate the pathophysiology of these CMDs, we generated microarray gene expression profiles of skeletal muscle from patients in various clinical stages. Despite diverse pathological changes, the correlation coefficient of overall gene expression among these samples was considerably high. We performed a multi-dimensional statistical analysis, the Distillation, to extract determinant genes that distinguish CMD muscle from normal controls. Up-regulated genes were primarily extracellular matrix (ECM) components, whereas down-regulated genes included structural components of mature muscle. These observations reflect active interstitial fibrosis with less active regeneration of muscle cell components in the CMDs, characteristics that are clearly distinct from those of DMD. Although the severity of fibrosis varied among the specimens tested, ECM gene expression was consistently high without substantial changes through the clinical course. Further, in situ hybridization showed more prominent ECM gene expression on muscle cells than on interstitial tissue cells, suggesting that ECM components are induced by regeneration process rather than by 'dystrophy.' These data imply that the etiology of FCMD and MDC1A differs from that of the chronic phase of classical muscular dystrophy, and the major pathophysiologic change in CMDs might instead result from primary active fibrosis. PMID:16487936

Taniguchi, Mariko; Kurahashi, Hiroki; Noguchi, Satoru; Sese, Jun; Okinaga, Takeshi; Tsukahara, Toshifumi; Guicheney, Pascale; Ozono, Keiichi; Nishino, Ichizo; Morishita, Shinichi; Toda, Tatsushi

2006-02-03

133

The 10 autosomal recessive limb-girdle muscular dystrophies  

Microsoft Academic Search

Fifteen forms of limb-girdle muscular dystrophies (5 autosomal dominant and 10 autosomal recessive) have already been found. The 10 genes responsible for the autosomal recessive forms, which account for more than 90% of the cases, had their product identified. This review will focus on the most recent data on autosomal recessive-limb-girdle muscular dystrophy and on our own experience of more

Mayana Zatz; Flavia de Paula; Alessandra Starling; Mariz Vainzof

2003-01-01

134

Dystrobrevin deficiency at the sarcolemma of patients with muscular dystrophy  

Microsoft Academic Search

Mutations in the genes encoding dystrophin or dystrophin-associated proteins are responsible for Duchenne muscular dystrophy or various forms of limb-girdle muscular dystrophies respectively. We have recently cloned the gene for the murine 87 kDa postsynaptic protein dystrobrevin, a dystrophin- associated protein. Anti-dystrobrevin antibodies stain the sarcolemma in normal skeletal muscle indicating that dystrobrevin co-localises with dystrophin and the dystrophin-associated protein

Laurent Metzinger; Derek J. Blake; Marian V. Squier; Louise V. B. Anderson; Anne E. Deconinck; Ralph Nawrotzki; David Hilton-Jones; Kay E. Davies

1997-01-01

135

Steroid Therapy and Cardiac Function in Duchenne Muscular Dystrophy  

Microsoft Academic Search

Duchenne muscular dystrophy leads to progressive deterioration in skeletal and cardiac muscle function. Steroids prolong ambulation\\u000a and improve respiratory muscle strength. The authors hypothesized that steroid treatment would stabilize cardiac muscle function.\\u000a Echocardiograms performed from 1997 to 2004 for 111 subjects 21 years of age or younger with Duchenne muscular dystrophy were\\u000a restrospectively reviewed. The medical record was reviewed for

L. W. Markham; R. L. Spicer; P. R. Khoury; B. L. Wong; K. D. Mathews; L. H. Cripe

2005-01-01

136

Vertebral fractures in boys with Duchenne muscular dystrophy.  

PubMed

Osteoporosis causes significant morbidity for boys with Duchenne muscular dystrophy. Corticosteroid therapy given to prolong mobility may increase the rate of osteoporosis and risk of fracture. This study of 33 boys with Duchenne muscular dystrophy determined retrospectively the incidence of vertebral fractures particularly after initiation of corticosteroids. A latency period of 40 months after commencement of steroids occurred before the first vertebral fracture appeared. However, by 100 months of treatment approximately 75% had sustained a vertebral fracture. PMID:12800730

Bothwell, J E; Gordon, K E; Dooley, J M; MacSween, J; Cummings, E A; Salisbury, S

2003-05-01

137

Pharmacologic and genetic therapy for childhood muscular dystrophies  

Microsoft Academic Search

The outstanding advances in the molecular characterization of muscle diseases, including muscular dystrophies, inflammatory\\u000a myopathies, and ion channel disorders, have resulted in the identification of potential targets for pharmacologic and genetic\\u000a therapy in the best characterized of these diseases. The most common myopathy in children, Duchenne muscular dystrophy (DMD),\\u000a is the focus of active pharmacologic clinical trials. Genetic transfer therapy

Diana M. Escolar; Cheryl G. Scacheri

2001-01-01

138

The Muscular Dystrophies: Distinct Pathogenic Mechanisms Invite Novel Therapeutic Approaches  

Microsoft Academic Search

Over the past decade, the enigmatic pathogenic mechanisms of the most common forms of muscular dystrophy have been defined.\\u000a In this report, the molecular defects for each of these disorders are fully described, demonstrating the potential for therapeutic\\u000a intervention. In facioscapulohumeral muscular dystrophy, recent findings implicate a stabilized DUX4 transcript within the contracted D4Z4 repeats, opening the door for an

Zarife Sahenk; Jerry R. Mendell

2011-01-01

139

RNAi Therapy for Dominant Muscular Dystrophies and Other Myopathies  

Microsoft Academic Search

\\u000a Over the last ?15 years, muscular dystrophy gene therapy strategies have been primarily aimed at replacing defective or missing\\u000a genes underlying recessive disorders, such as Duchenne muscular dystrophy. These gene replacement strategies are typically\\u000a not indicated for treating dominant diseases; instead, patients bearing dominant mutations would likely benefit from reduction\\u000a or elimination of the abnormal allele. Until very recently, there

Lindsay M. Wallace; Sara E. Garwick; Scott Q. Harper

140

Dystrophin in frameshift deletion patients with Becker Muscular Dystrophy  

Microsoft Academic Search

In a previous study the authors identified 14 cases with Duchenne muscular dystrophy (DMD) or its milder variant, Becker muscular dystrophy (BMD), with a deletion of exons 3-7, a deletion that would be expected to shift the translational reading frame of the mRNA and give a severe phenotype. They have examined dystrophin and its mRNA from muscle biopsies of seven

S. B. Gangopadhyay; P. N. Ray; R. G. Worton; T. G. Sherratt; J. Z. Heckmatt; V. Dubowitz; P. N. Strong; G. Miller; M. Shokeir

1992-01-01

141

Membrane protein kinase alteration in Duchenne muscular dystrophy  

Microsoft Academic Search

DUCHENNE muscular dystrophy (DuD) is the severe form of heredo-familial muscular dystrophy inherited as a sex linked recessive trait. The primary clinical manifestations are progressive muscle weakness usually starting in the pelvic girdle accompanied by hypertrophy in the calf musculature. Significant cardiac abnormalities and mental retardation have also been reported. The primary inherited metabolic defect is unknown1. Elevated levels of

Allen D. Roses; Michael H. Herbstreith; Stanley H. Appel

1975-01-01

142

Common pathological mechanisms in mouse models for muscular dystrophies  

Microsoft Academic Search

Duchenne\\/Becker and limb-girdle muscular dystrophies share clinical symptoms like muscle weakness and wasting but differ in clinical presentation and severity. To get a closer view on the differentiating molecular events responsible for the muscular dystrophies, we have carried out a comparative gene expression profiling of hindlimb muscles of the following mouse models: dystrophin-deficient (mdx, mdx3cv), sarcoglycan-deficient (Sgca null, Sgcb null,

R. Turk; E. Sterrenburg; E. J. de Meijer; R. X. de Menezes

2005-01-01

143

Muscular Dystrophy Gene Therapy in Small Animal Models  

Microsoft Academic Search

\\u000a Muscular dystrophies are inherited neuromuscular disorders characterized by progressive muscle loss and weakness. The morbidity\\u000a and fatality associated with the diseases and a lack of effective treatment have prompted urgent search for novel therapeutics.\\u000a Gene therapy is one of the frontiers. Currently, adeno-associated viral (AAV) vector-mediated gene transfer offers a powerful\\u000a tool for muscular dystrophy gene therapy for both skeletal

Chunping Qiao; Xiao Xiao

144

A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy  

Microsoft Academic Search

Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy in adults that is foremost characterized by progressive wasting of muscles in the upper body. FSHD is associated with contraction of D4Z4 macrosatellite repeats on chromosome 4q35, but this contraction is pathogenic only in certain ``permissive'' chromosomal backgrounds. Here, we show that FSHD patients carry specific single-nucleotide polymorphisms in

Richard J. L. F. Lemmers; Patrick J. van der Vliet; Rinse Klooster; Sabrina Sacconi; Pilar Camaño; Johannes G. Dauwerse; Lauren Snider; Kirsten R. Straasheijm; Gert Jan van Ommen; George W. Padberg; Daniel G. Miller; Stephen J. Tapscott; Rabi Tawil; Rune R. Frants; Silvère M. van der Maarel

2010-01-01

145

Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy  

Microsoft Academic Search

Fukuyama congenital muscular dystrophy (FCMD), muscle-eye-brain disease (MEB), and Walker-Warburg syndrome are congenital muscular dystrophies (CMDs) with associated developmental brain defects. Mutations reported in genes of FCMD and MEB patients suggest that the genes may be involved in protein glycosylation. Dystroglycan is a highly glycosylated component of the muscle dystrophin-glycoprotein complex that is also expressed in brain, where its function

Steven A. Moore; Fumiaki Saito; Jianguo Chen; Daniel E. Michele; Michael D. Henry; Albee Messing; Ronald D. Cohn; Susan E. Ross-Barta; Steve Westra; Roger A. Williamson; Toshinori Hoshi; Kevin P. Campbell

2002-01-01

146

Wnt7a treatment ameliorates muscular dystrophy.  

PubMed

Duchenne muscular dystrophy (DMD) is a devastating genetic muscular disorder of childhood marked by progressive debilitating muscle weakness and wasting, and ultimately death in the second or third decade of life. Wnt7a signaling through its receptor Fzd7 accelerates and augments regeneration by stimulating satellite stem cell expansion through the planar cell polarity pathway, as well as myofiber hypertrophy through the AKT/mammalian target of rapamycin (mTOR) anabolic pathway. We investigated the therapeutic potential of the secreted factor Wnt7a for focal treatment of dystrophic DMD muscles using the mdx mouse model, and found that Wnt7a treatment efficiently induced satellite cell expansion and myofiber hypertrophy in treated mucles in mdx mice. Importantly, Wnt7a treatment resulted in a significant increase in muscle strength, as determined by generation of specific force. Furthermore, Wnt7a reduced the level of contractile damage, likely by inducing a shift in fiber type toward slow-twitch. Finally, we found that Wnt7a similarly induced myotube hypertrophy and a shift in fiber type toward slow-twitch in human primary myotubes. Taken together, our findings suggest that Wnt7a is a promising candidate for development as an ameliorative treatment for DMD. PMID:23185011

von Maltzahn, Julia; Renaud, Jean-Marc; Parise, Gianni; Rudnicki, Michael A

2012-11-26

147

Muscular dystrophies at different ages: metabolic and endocrine alterations.  

PubMed

Common metabolic and endocrine alterations exist across a wide range of muscular dystrophies. Skeletal muscle plays an important role in glucose metabolism and is a major participant in different signaling pathways. Therefore, its damage may lead to different metabolic disruptions. Two of the most important metabolic alterations in muscular dystrophies may be insulin resistance and obesity. However, only insulin resistance has been demonstrated in myotonic dystrophy. In addition, endocrine disturbances such as hypogonadism, low levels of testosterone, and growth hormone have been reported. This eventually will result in consequences such as growth failure and delayed puberty in the case of childhood dystrophies. Other consequences may be reduced male fertility, reduced spermatogenesis, and oligospermia, both in childhood as well as in adult muscular dystrophies. These facts all suggest that there is a need for better comprehension of metabolic and endocrine implications for muscular dystrophies with the purpose of developing improved clinical treatments and/or improvements in the quality of life of patients with dystrophy. Therefore, the aim of this paper is to describe the current knowledge about of metabolic and endocrine alterations in diverse types of dystrophinopathies, which will be divided into two groups: childhood and adult dystrophies which have different age of onset. PMID:22701119

Cruz Guzmán, Oriana Del Rocío; Chávez García, Ana Laura; Rodríguez-Cruz, Maricela

2012-06-03

148

Muscular Dystrophies at Different Ages: Metabolic and Endocrine Alterations  

PubMed Central

Common metabolic and endocrine alterations exist across a wide range of muscular dystrophies. Skeletal muscle plays an important role in glucose metabolism and is a major participant in different signaling pathways. Therefore, its damage may lead to different metabolic disruptions. Two of the most important metabolic alterations in muscular dystrophies may be insulin resistance and obesity. However, only insulin resistance has been demonstrated in myotonic dystrophy. In addition, endocrine disturbances such as hypogonadism, low levels of testosterone, and growth hormone have been reported. This eventually will result in consequences such as growth failure and delayed puberty in the case of childhood dystrophies. Other consequences may be reduced male fertility, reduced spermatogenesis, and oligospermia, both in childhood as well as in adult muscular dystrophies. These facts all suggest that there is a need for better comprehension of metabolic and endocrine implications for muscular dystrophies with the purpose of developing improved clinical treatments and/or improvements in the quality of life of patients with dystrophy. Therefore, the aim of this paper is to describe the current knowledge about of metabolic and endocrine alterations in diverse types of dystrophinopathies, which will be divided into two groups: childhood and adult dystrophies which have different age of onset.

Cruz Guzman, Oriana del Rocio; Chavez Garcia, Ana Laura; Rodriguez-Cruz, Maricela

2012-01-01

149

Morphologic imaging in muscular dystrophies and inflammatory myopathies  

Microsoft Academic Search

Objective  To determine if magnetic resonance imaging (MR imaging) is useful in the diagnostic workup of muscular dystrophies and idiopathic\\u000a inflammatory myopathies for describing the topography of muscle involvement.\\u000a \\u000a \\u000a \\u000a \\u000a Materials and methods  MR imaging was performed in 31 patients: 8 with dystrophic myotony types 1 (n?=?4) or 2 (n?=?4); 11 with limb-girdle muscular dystrophy, including dysferlinopathy, calpainopathy, sarcoglycanopathy, and dystrophy\\u000a associated with

Adrian Degardin; David Morillon; Arnaud Lacour; Anne Cotten; Patrick Vermersch; Tanya Stojkovic

2010-01-01

150

Bone mineral density and bone metabolism in Duchenne muscular dystrophy  

Microsoft Academic Search

Very few studies on bone mineral density and bone metabolism in Duchenne muscular dystrophy (DMD) have been reported. DMD is a severe, progressive muscular disease resulting in death at a young age. No specific therapies are available, but corticosteroids induce improvement and slower progression of the disease. However, long-term steroid therapy is a serious risk factor for osteoporosis. This study

M. L. Bianchi; A. Mazzanti; E. Galbiati; S. Saraifoger; A. Dubini; F. Cornelio; L. Morandi

2003-01-01

151

Severe phenotype in infantile facioscapulohumeral muscular dystrophy.  

PubMed

While much is known about the clinical course of adult FSHD, the third most common inherited muscular dystrophy, data on the "infantile phenotype" and especially on the progression of the disease in children are limited. We have followed a cohort of 7 patients with infantile FSHD for 9-25 years and here report the clinical and genetic findings in this group. Infantile FSHD is relatively rare, amounting to 4% of all of our FSHD patients. Despite some variability in the progression, infantile FSHD has a more consistent phenotype than adult FSHD. Although they had normal motor milestones, all patients showed facial weakness from early childhood, and subsequently were severely affected with rapid progression of the disease, marked muscular wasting, weakness, and hyperlordosis. None of the patients have shown signs of nocturnal hypoventilation or cardiomyopathy so far. No correlation was found between sex and the severity of phenotype whereas all but one patient had very short fragment sizes of the D4Z4 repeat. Only two patients had a de novo mutation: 3 patients inherited the mutation from a parent with somatic mosaicism, and one was inherited from a parent with classical adult FSHD. One patient was unusual in having one allele inherited from his father who showed somatic mosaicism and one allele with an additional de novo mutation. We conclude that infantile FSHD is a severe and rapidly progressive disease, and this needs to be taken into account in the advice given to patients diagnosed in early childhood. However, our data also suggest that the risk to an individual with classical FSHD of having a child with the infantile form is low. PMID:16934468

Klinge, Lars; Eagle, Michelle; Haggerty, Irene D; Roberts, Catherine E; Straub, Volker; Bushby, Kate M

2006-08-24

152

Early neurodevelopmental assessment in Duchenne muscular dystrophy.  

PubMed

The aim of this study was to assess neurodevelopmental profile in young boys affected by Duchenne muscular dystrophy and to establish the correlation between neurodevelopmental findings, and the type and site of mutations. A structured neurodevelopmental assessment (Griffiths Scale of Mental Development) was performed in 81 DMD boys before the age of four years (range: 7-47 months). The mean total DQ was 87 (SD 15.3). Borderline DQ (between 70 and 84) was found in 32% and DQ below 70 in 12.3% of the patients. Children with mutations upstream or in exon 44 had higher DQ than those with mutations downstream exon 44 which are associated with involvement of dystrophin isoforms expressed at high levels in brain. The difference was significant for total and individual subscale DQ with the exception of the locomotor subscale. Items, such as ability to run fast, or getting up from the floor consistently failed in all children, irrespective of the age or of the site of mutation. Our results help to understand the possible different mechanisms underlying the various aspects of neurodevelopmental delay, suggesting that the involvement of brain dystrophin isoforms may cause a delay in the maturation of coordination and dexterity. PMID:23535446

Pane, Marika; Scalise, Roberta; Berardinelli, Angela; D'Angelo, Grazia; Ricotti, Valeria; Alfieri, Paolo; Moroni, Isabella; Hartley, Louise; Pera, Maria Carmela; Baranello, Giovanni; Catteruccia, Michela; Casalino, Tiziana; Romeo, Domenico M; Graziano, Alessandra; Gandioli, Claudia; Bianco, Flaviana; Mazzone, Elena Stacy; Lombardo, Maria Elena; Scoto, Mariacristina; Sivo, Serena; Palermo, Concetta; Gualandi, Francesca; Sormani, Maria Pia; Ferlini, Alessandra; Bertini, Enrico; Muntoni, Francesco; Mercuri, Eugenio

2013-03-25

153

Indications for a Novel Muscular Dystrophy Pathway  

PubMed Central

?-Filamin, also called ABP-L, is a filamin isoform that is specifically expressed in striated muscles, where it is predominantly localized in myofibrillar Z-discs. A minor fraction of the protein shows subsarcolemmal localization. Although ?-filamin has the same overall structure as the two other known isoforms, it is the only isoform that carries a unique insertion in its immunoglobulin (Ig)-like domain 20. Sequencing of the genomic region encoding this part of the molecule shows that this insert is encoded by an extra exon. Transient transfections of the insert-bearing domain in skeletal muscle cells and cardiomyocytes show that this single domain is sufficient for targeting to developing and mature Z-discs. The yeast two-hybrid method was used to identify possible binding partners for the insert-bearing Ig-like domain 20 of ?-filamin. The two Ig-like domains of the recently described ?-actinin–binding Z-disc protein myotilin were found to interact directly with this filamin domain, indicating that the amino-terminal end of ?-filamin may be indirectly anchored to ?-actinin in the Z-disc via myotilin. Since defects in the myotilin gene were recently reported to cause a form of autosomal dominant limb-girdle muscular dystrophy, our findings provide a further contribution to the molecular understanding of this disease.

van der Ven, Peter F.M.; Wiesner, Sebastian; Salmikangas, Paula; Auerbach, Daniel; Himmel, Mirko; Kempa, Stefan; Hayess, Katrin; Pacholsky, Dirk; Taivainen, Anu; Schroder, Rolf; Carpen, Olli; Furst, Dieter O.

2000-01-01

154

Lipomatous muscular 'dystrophy' of Piedmontese cattle.  

PubMed

Lipomatous myopathy is a degenerative muscle pathology characterized by the substitution of muscle cells with adipose tissue, sporadically reported in cattle, pigs, and rarely in sheep, horses and dogs. This study investigated the pathology of this myopathy in 40 muscle samples collected from regularly slaughtered Piedmontese cattle living in Piedmont region (Italy). None of the animals showed clinical signs of muscular disease. Muscle specimens were submitted to histological and enzymatic investigations. Gross pathology revealed a different grade of infiltration of adipose tissue, involving multiple or single muscles. The most affected regions were the ventral abdomen and the shoulders, especially the cutaneous muscles and the muscles of the thoracic group. Morphological staining revealed an infiltration of adipose tissue varying in distribution and severity, changes in muscle fibre size and increased number of fibres with centrally located nuclei, suggesting muscle degeneration-regeneration. Necrosis and non-suppurative inflammatory cells were also seen. Furthermore, proliferation of connective tissue and non-specific myopathic changes were present. Chemical and physical characteristics of the affected tissue were also evaluated. The authors discuss about the aetiopathogenesis and classification of this muscle disorder whose histological lesions were similar to those reported in human dystrophies. PMID:22717052

Biasibetti, E; Amedeo, S; Brugiapaglia, A; Destefanis, G; Di Stasio, L; Valenza, F; Capucchio, M T

2012-04-27

155

[Database for patients with Duchenne muscular dystrophy].  

PubMed

We had a plan to arrange database for patients with Duchenne muscular dystrophy in Japan. The purpose of this projects will make it possible to design accurate and serial evaluation of patients and conduct therapeutic trial. The items of input are composed of two cards. One card is basic card which fills out mainly patients' basic and genetic informations, the other is course card which records symptoms, muscle strength, joint range of motion, laboratory studies including pulmonary function testing and therapeutic trials. These cards are written by physicians of dystrophic wards in national hospital twice a year and are sent to the statistical coordinating center of database. On the other hand outputs include annual report and optional output which are requested by each investigator. Now 519 basic cards and 1026 course cards have completed. In this paper we tried to output about some results of the data obtained. These outputs include the age of initial gait and difficulty in walking, mean muscle strength by functional grade and the change of muscle strength during the administration of some drugs. PMID:2085925

Fukunaga, H; Ishiduka, T; Sato, M; Igata, A; Nishitani, H

1990-11-01

156

Molecular analysis of facioscapulohumeral muscular dystrophy (FSHD)  

SciTech Connect

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by progressive muscle weakness. The disease locus maps to 4q35 and is associated with a de novo DNA rearrangement, detected by a probe p13E-11 (D4F104S1) which maps proximal to the disease locus. An informative distal flanking marker for this condition is still required. Using p13E-11, we have analyzed 35 FSHD families in which the disease is apparently associated with a new mutation. Twenty three of these cases were found to have a smaller rearranged DNA fragment which was not present in either of the parents. Pulsed-field gel analysis of 5 of these families also revealed evidence of DNA deletion. During the course of this study, we identified one case with a DNA rearrangement which was also present in the unaffected mother, but at very low intensity. This finding has been confirmed by pulsed-field gel analysis, and indicates that the mother is probably a gonosomal mosaic. In order to saturate the FSHD region with new DNA markers, a laser microdissection and microcloning technique was used to construct a genomic library from the distal end of chromosome 4. Of the 72 microclones analyzed, 42 mapped into the relevant 4q35 region. 4 sequences were conserved and may be considered potential candidate genes for FSHD. The microclones mapping to 4q35 are under study to identify additional polymorphic markers for the FSHD region.

Upadhyaya, M.; Maynard, J.; Osborn, M. [Institute of Medical Genetics, Cardiff (United Kingdom)] [and others

1994-09-01

157

Genetic therapeutic approaches for Duchenne muscular dystrophy.  

PubMed

Despite an expansive wealth of research following the discovery of the DMD gene 25 years ago, there is still no curative treatment for Duchenne muscular dystrophy. However, there are currently many promising lines of research, including cell-based therapies and pharmacological reagents to upregulate dystrophin via readthrough of nonsense mutations or by upregulation of the dystrophin homolog utrophin. Here we review genetic-based therapeutic strategies aimed at the amelioration of the DMD phenotype. These include the reintroduction of a copy of the DMD gene into an affected tissue by means of a viral vector; correction of the mutated DMD transcript by antisense oligonucleotide-induced exon skipping to restore the open reading frame; and direct modification of the DMD gene at a chromosomal level through genome editing. All these approaches are discussed in terms of the more recent advances, and the hurdles to be overcome if a comprehensive and effective treatment for DMD is to be found. These hurdles include the need to target all musculature of the body. Therefore any potential treatment would need to be administered systemically. In addition, any treatment needs to have a long-term effect, with the possibility of readministration, while avoiding any potentially detrimental immune response to the vector or transgene. PMID:22647146

Foster, Helen; Popplewell, Linda; Dickson, George

2012-07-01

158

Muscular Dystrophy Research and Education Plan for the National Institutes of Health.  

National Technical Information Service (NTIS)

The muscular dystrophies are a group of chronic diseases primarily characterized by weakness and progressive degeneration of skeletal muscles. In December 2001, the President signed into law the Muscular Dystrophy Community Assistance, Research and Educat...

2004-01-01

159

Neurocognitive profiles in Duchenne muscular dystrophy and gene mutation site.  

PubMed

The presence of nonprogressive cognitive impairment is recognized as a common feature in a substantial proportion of patients with Duchenne muscular dystrophy. To investigate the possible role of mutations along the dystrophin gene affecting different brain dystrophin isoforms and specific cognitive profiles, 42 school-age children affected with Duchenne muscular dystrophy, subdivided according to sites of mutations along the dystrophin gene, underwent a battery of tests tapping a wide range of intellectual, linguistic, and neuropsychologic functions. Full-scale intelligence quotient was approximately 1 S.D. below the population average in the whole group of dystrophic children. Patients with Duchenne muscular dystrophy and mutations located in the distal portion of the dystrophin gene (involving the 140-kDa brain protein isoform, called Dp140) were generally more severely affected and expressed different patterns of strengths and impairments, compared with patients with Duchenne muscular dystrophy and mutations located in the proximal portion of the dystrophin gene (not involving Dp140). Patients with Duchenne muscular dystrophy and distal mutations demonstrated specific impairments in visuospatial functions and visual memory (which seemed intact in proximally mutated patients) and greater impairment in syntactic processing. PMID:22000308

D'Angelo, Maria Grazia; Lorusso, Maria Luisa; Civati, Federica; Comi, Giacomo Pietro; Magri, Francesca; Del Bo, Roberto; Guglieri, Michela; Molteni, Massimo; Turconi, Anna Carla; Bresolin, Nereo

2011-11-01

160

Assessment of disease activity in muscular dystrophies by noninvasive imaging.  

PubMed

Muscular dystrophies are a class of disorders that cause progressive muscle wasting. A major hurdle for discovering treatments for the muscular dystrophies is a lack of reliable assays to monitor disease progression in animal models. We have developed a novel mouse model to assess disease activity noninvasively in mice with muscular dystrophies. These mice express an inducible luciferase reporter gene in muscle stem cells. In dystrophic mice, muscle stem cells activate and proliferate in response to muscle degeneration, resulting in an increase in the level of luciferase expression, which can be monitored by noninvasive, bioluminescence imaging. We applied this noninvasive imaging to assess disease activity in a mouse model of the human disease limb girdle muscular dystrophy 2B (LGMD2B), caused by a mutation in the dysferlin gene. We monitored the natural history and disease progression in these dysferlin-deficient mice up to 18 months of age and were able to detect disease activity prior to the appearance of any overt disease manifestation by histopathological analyses. Disease activity was reflected by changes in luciferase activity over time, and disease burden was reflected by cumulative luciferase activity, which paralleled disease progression as determined by histopathological analysis. The ability to monitor disease activity noninvasively in mouse models of muscular dystrophy will be invaluable for the assessment of disease progression and the effectiveness of therapeutic interventions. PMID:23619364

Maguire, Katie K; Lim, Leland; Speedy, Sedona; Rando, Thomas A

2013-04-24

161

TRIM proteins in therapeutic membrane repair of muscular dystrophy.  

PubMed

Muscular dystrophy represents a major unmet medical need; only palliative treatments exist for this group of debilitating diseases. Because multiple forms of muscular dystrophy arise from compromised sarcolemmal membrane integrity, a therapeutic approach that can target this loss of membrane function could be applicable to a number of these distinct diseases.One promising therapeutic approach involves the process the cell uses to repair injuries to the plasma membrane. Recent discoveries of genes associated with the membrane repair process provide an opportunity to promote this process as a way to treat muscular dystrophy. One such gene is mitsugumin 53 (MG53), a member of the tripartite motif (TRIM) family of proteins (TRIM72), which is an essential component of the membrane repair pathway in muscle. Recent results indicate that MG53/TRIM72 protein can be directly applied as a therapeutic agent to increase membrane repair capacity of many cell types and treat some aspects of the disease in mouse models of muscular dystrophy. There is great potential for the use of recombinant human MG53 in treating muscular dystrophy and other diseases in which compromised membrane integrity contributes to the disease. Other TRIM family proteins may provide additional targets for therapeutic intervention in similar disease states. PMID:23699904

Alloush, Jenna; Weisleder, Noah

2013-07-01

162

A case of Fukuyama-type congenital muscular dystrophy with a very mild mental deficit  

Microsoft Academic Search

A boy had the clinical features of congenital muscular dystrophy with a very mild mental deficit. A muscle biopsy at one year of age showed the typical findings of Fukuyama-type congenital muscular dystrophy, including selective loss of immunoreactions for alpha dystroglycan. Magnetic resonance imaging showed no findings suggestive of migration disorders. The diagnosis of Fukuyama-type congenital muscular dystrophy was confirmed

Naomi Hino-Fukuyo; Kazuhiro Haginoya; Yukiko K. Hayashi; Ichizo Nishino; Terumi Murakami; Ikuya Nonaka; Kaoru Togashi; Souichiro Tanaka; Masaru Takayanagi; Hiroyuki Yokoyama; Osamu Sakamoto; Toshiaki Abe; Tatsushi Toda; Kazuie Iinuma

2006-01-01

163

Molecular deletion patterns in Duchenne and Becker muscular dystrophy patients from KwaZulu Natal  

Microsoft Academic Search

There exists much phenotypic heterogeneity in Duchenne muscular dystrophy and its allelic variant, Becker muscular dystrophy. The molecular findings on 53 patients with Duchenne and 15 patients with Becker type muscular dystrophy in KwaZulu Natal, South Africa are reported. Multiplex PCR was performed using primers targeting 18 hot-spot exons throughout the dystrophin gene. Analysis of the multiplex PCR data revealed

K. D. Hallwirth Pillay; P. L. A. Bill; S. Madurai; L. Mubaiwa; P. Rapiti

2007-01-01

164

Feasibility of neonatal screening for Duchenne muscular dystrophy.  

PubMed Central

During the period November 1976 to September 1980, 2703 babies born in one Edinburgh hospital were screened in the neonatal period by estimation of their serum creatine kinase levels for Duchenne muscular dystrophy. Among the 2336 male babies tested, none proved to be affected and only 16 required second specimens to be obtained. Overall the false positive rate in the study was 0.78%. This study confirms that neonatal screening for Duchenne muscular dystrophy is feasible in a British hospital setting and is here most conveniently carried out on the 5th day of life along with routine testing for phenylketonuria.

Skinner, R; Emery, A E; Scheuerbrandt, G; Syme, J

1982-01-01

165

Rhabdomyolysis in association with Duchenne’s muscular dystrophy  

Microsoft Academic Search

Purpose  To present a case of rhabdomyolysis which developed in a child with a known history of Duchenne’s muscular dystrophy, following\\u000a an anesthetic which included sevoflurane.\\u000a \\u000a \\u000a \\u000a Clinical features  An 11 yr old boy with a known history of Duchenne’s muscular dystrophy underwent anesthesia for strabismus repair. The anesthetic\\u000a consisted of sevoflurane and nitrous oxide without the use of a muscle relaxant. His

Ryoji Obata; Yasuhiro Yasumi; Akira Suzuki; Yoshiki Nakajima; Shigehito Sato

1999-01-01

166

The paradox of muscle hypertrophy in muscular dystrophy.  

PubMed

Mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophy in humans and syndromes in mice, dogs, and cats. Affected humans and dogs have progressive disease that leads primarily to muscle atrophy. Mdx mice progress through an initial phase of muscle hypertrophy followed by atrophy. Cats have persistent muscle hypertrophy. Hypertrophy in humans has been attributed to deposition of fat and connective tissue (pseudohypertrophy). Increased muscle mass (true hypertrophy) has been documented in animal models. Muscle hypertrophy can exaggerate postural instability and joint contractures. Deleterious consequences of muscle hypertrophy should be considered when developing treatments for muscular dystrophy. PMID:22239881

Kornegay, Joe N; Childers, Martin K; Bogan, Daniel J; Bogan, Janet R; Nghiem, Peter; Wang, Jiahui; Fan, Zheng; Howard, James F; Schatzberg, Scott J; Dow, Jennifer L; Grange, Robert W; Styner, Martin A; Hoffman, Eric P; Wagner, Kathryn R

2012-02-01

167

Torn apart: membrane rupture in muscular dystrophies and associated cardiomyopathies  

PubMed Central

Muscular dystrophies are often caused by mutations in cytoskeletal proteins that render cells more susceptible to strain-induced injury in mechanically active tissues such as skeletal or cardiac muscle. In this issue of the JCI, Han et al. report that dysferlin participates in membrane resealing in cardiomyocytes and that exercise results in increased membrane damage and disturbed cardiac function in dysferlin-deficient mice (see the related article beginning on page 1805). Thus, in addition to repetitive membrane damage, inadequate membrane repair may participate in the pathogenesis of muscular dystrophies and cardiomyopathies.

Lammerding, Jan; Lee, Richard T.

2007-01-01

168

Torn apart: membrane rupture in muscular dystrophies and associated cardiomyopathies.  

PubMed

Muscular dystrophies are often caused by mutations in cytoskeletal proteins that render cells more susceptible to strain-induced injury in mechanically active tissues such as skeletal or cardiac muscle. In this issue of the JCI, Han et al. report that dysferlin participates in membrane resealing in cardiomyocytes and that exercise results in increased membrane damage and disturbed cardiac function in dysferlin-deficient mice (see the related article beginning on page 1805). Thus, in addition to repetitive membrane damage, inadequate membrane repair may participate in the pathogenesis of muscular dystrophies and cardiomyopathies. PMID:17607350

Lammerding, Jan; Lee, Richard T

2007-07-01

169

A study of FHL1, BAG3, MATR3, PTRF and TCAP in Australian muscular dystrophy patients  

Microsoft Academic Search

FHL1, BAG3, MATR3 and PTRF are recently identified myopathy genes associated with phenotypes that overlap muscular dystrophy. TCAP is a rare reported cause of muscular dystrophy not routinely screened in most centres. We hypothesised that these genes may account for patients with undiagnosed forms of muscular dystrophy in Australia. We screened a large cohort of muscular dystrophy patients for abnormalities

Leigh B. Waddell; Jenny Tran; Xi F. Zheng; Carsten G. Bönnemann; Ying Hu; Frances J. Evesson; Monkol Lek; Susan Arbuckle; Min-Xia Wang; Robert L. Smith; Kathryn N. North; Nigel F. Clarke

2011-01-01

170

Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): Case Definition in Surveillance for Childhood-Onset Duchenne\\/Becker Muscular Dystrophy  

Microsoft Academic Search

The Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) is a multisite collaboration to determine the prevalence of childhood-onset Duchenne\\/Becker muscular dystrophy and to characterize health care and health outcomes in this population. MD STARnet uses medical record abstraction to identify patients with Duchenne\\/Becker muscular dystrophy born January 1, 1982 or later who resided in 1 of the participating

Katherine D. Mathews; Chris Cunniff; Jiji R. Kantamneni; Emma Ciafaloni; Timothy Miller; Dennis Matthews; Valerie Cwik; Charlotte Druschel; Lisa Miller; F. John Meaney; John Sladky; Paul A. Romitti

2010-01-01

171

Laminin111: A Potential Therapeutic Agent for Duchenne Muscular Dystrophy  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD) still needs effective treatments, and myoblast transplantation (MT) is considered as an approach to repair damaged skeletal muscles. DMD is due to the complete loss of dystrophin from muscles. The lack of link between the contracting apparatus and the extracellular matrix leads to frequent damage to the sarcolemma triggering muscle fiber necrosis. Laminins are major proteins

Sébastien Goudenege; Yann Lamarre; Nicolas Dumont; Joël Rousseau; Jérôme Frenette; Daniel Skuk; Jacques P Tremblay

2010-01-01

172

Presence of mechanical dyssynchrony in duchenne muscular dystrophy  

Microsoft Academic Search

BACKGROUND: Cardiac dysfunction in boys with Duchenne muscular dystrophy (DMD) is a leading cause of death. Cardiac resynchronization therapy (CRT) has been shown to dramatically decrease mortality in eligible adult population with congestive heart failure. We hypothesized that mechanical dyssynchrony is present in DMD patients and that cardiovascular magnetic resonance (CMR) may predict CRT efficacy. METHODS: DMD patients (n =

Kan N Hor; Janaka P Wansapura; Hussein R Al-Khalidi; William M Gottliebson; Michael D Taylor; Richard J Czosek; Sherif F Nagueh; Nandakishore Akula; Eugene S Chung; Woodrow D Benson; Wojciech Mazur

2011-01-01

173

Congenital nutritional muscular dystrophy in a beef calf  

PubMed Central

A 13-hour-old Aberdeen-Angus was involuntarily recumbent since birth. Congenital nutritional muscular dystrophy was suspected based on clinical findings, increased serum creatine kinase, and decreased serum vitamin E and selenium levels. Recovery followed after supportive therapy and parenteral vitamin E and selenium. Reports of this disease in newborn calves are unusual.

Abutarbush, Sameeh M.; Radostits, Otto M.

2003-01-01

174

Swallow Characteristics in Patients with Oculopharyngeal Muscular Dystrophy  

ERIC Educational Resources Information Center

Purpose: This prospective investigation evaluates oral weakness and its impact on swallow function, weight, and quality of life in patients with oculopharyngeal muscular dystrophy (OPMD). Method: Intraoral pressure, swallow pressure, and endurance were measured using an Iowa Oral Performance Instrument in participants with OPMD and matched…

Palmer, Phyllis M.; Neel, Amy T.; Sprouls, Gwyneth; Morrison, Leslie

2010-01-01

175

Cardiomyopathy is independent of skeletal muscle disease in muscular dystrophy  

Microsoft Academic Search

Dystrophin and its associated proteins, the sarcoglycans, are normally expressed in heart and skeletal muscle. Mutations that alter the expression of these membrane-associated proteins lead to muscular dystrophy (MD) and cardiomyopathy in humans. Because of the timing and nature of the accompanying cardiomyopathy, it has been suggested that cardiomyopathy develops as a secondary consequence of skeletal muscle dysfunction in the

Xiaolei Zhu; Matthew T. Wheeler; Michele Hadhazy; Man-Yee J. Lam

2002-01-01

176

Swallow Characteristics in Patients with Oculopharyngeal Muscular Dystrophy  

ERIC Educational Resources Information Center

|Purpose: This prospective investigation evaluates oral weakness and its impact on swallow function, weight, and quality of life in patients with oculopharyngeal muscular dystrophy (OPMD). Method: Intraoral pressure, swallow pressure, and endurance were measured using an Iowa Oral Performance Instrument in participants with OPMD and matched…

Palmer, Phyllis M.; Neel, Amy T.; Sprouls, Gwyneth; Morrison, Leslie

2010-01-01

177

Revertant fibres: a possible genetic therapy for Duchenne muscular dystrophy?  

Microsoft Academic Search

The mdx mouse, an animal model used to study Duchenne muscular dystrophy (DMD), has a nonsense mutation in exon 23 of the dystrophin gene which should result in a truncated protein that cannot be correctly localized at the sarcolemma of the muscle fibres. Immunohistochemical staining with anti-dystrophin antibodies had shown that while most of the muscle tissue was dystrophin-negative, a

Stephen D Wilton; Danielle E Dye; Lori M Blechynden; Nigel G Laing

1997-01-01

178

Preclinical Studies for Gene Therapy of Duchenne Muscular Dystrophy  

Microsoft Academic Search

The muscular dystrophies are a diverse group of genetic disorders without an effective treatment. Because they are caused by mutations in various genes, the most direct way to treat them involves correcting the underlying gene defect (ie, gene therapy). Such a gene therapy approach involves delivering a therapeutic gene cassette to essentially all the muscles of the body in a

Guy L. Odom; Glen B. Banks; Brian R. Schultz; Paul Gregorevic; Jeffrey S. Chamberlain

2010-01-01

179

Feeding problems in merosin deficient congenital muscular dystrophy  

Microsoft Academic Search

Feeding difficulties were assessed in 14 children (age range 2–14 years) with merosin deficient congenital muscular dystrophy, a disease characterised by severe muscle weakness and inability to achieve independent ambulation. Twelve of the 14 children were below the 3rd centile for weight. On questioning, all parents thought their child had difficulty chewing, 12 families modified the diet, and 13 children

J Philpot; A Bagnall; C King; V Dubowitz; F Muntoni

1999-01-01

180

Nonmuscular involvement in merosin-negative congenital muscular dystrophy  

Microsoft Academic Search

The spectrum of nonmuscular involvement in six children with merosin-negative congenital muscular dystrophy is described. In all children, biochemical, neuroradiologic, cardiac, and neurophysiologic studies were performed. Cerebral structures that were myelinated at gestation, including internal capsule, corpus callosum, brainstem, and cerebellar white matter, demonstrated no abnormalities, whereas the periventricular and subcortical white matter, which were myelinated in the first postnatal

H. Jacobus Gilhuis; Hans J ten Donkelaar; Ronald B Tanke; Dick M Vingerhoets; Machiel J Zwarts; Aad Verrips; Fons J. M Gabreëls

2002-01-01

181

Brain alterations in the classical form of congenital muscular dystrophy  

Microsoft Academic Search

In the classical form of congenital muscular dystrophy (CMD), subclinical brain involvement is frequent. In order to establish the natural evolution of CNS alterations in this type of CMD, the cerebral functions of 12 cases were examined longitudinally for a mean period of 8 years. There were 7 boys and 5 girls, with a mean age of 5 years at

Carlo P. Trevisan; Francesco Martinello; Emilia Ferruzza; Marina Fanin; Martine Chevallay; Fernando M. S. Tomé

1996-01-01

182

Congenital muscular dystrophy: A review of the literature  

Microsoft Academic Search

Congenital muscular dystrophy (CMD) is a condition in which there are already at birth, marked hypotonia, generalized muscle weakness and frequently multiple contractures. CMD has recently been classified into four categories: CMD I, the classical or ‘pure’ CMD without severe impairment of intellectual development; CMD II, the Fukuyama type CMD with muscle and structural brain abnormalities; CMD III and IV

Q. H. Leyten; F. J. M. Gabreëls; W. O. Renier; H. J. ter Laak

1996-01-01

183

Variable histomorphology of muscle in congenital muscular dystrophy  

Microsoft Academic Search

Congenital muscular dystrophy (CMD) is a relatively uncommon disease with a controversial nosological status. That collagen synthesis could be the primary abnormality has been suggested earlier (Fidzianska et al., 1982). Amongst eighteen cases of CMD diagnosed during the past twelve years, muscle biopsy in three cases revealed prominence of myofibre necrosis and phagocytosis, and serum CPK was markedly elevated suggesting

Sarala Das; N Gayathri; M Gourie-Devi; Anisya-Vasanth; Y Ramamohan

1997-01-01

184

Changes of laminin ?2 chain expression in congenital muscular dystrophy  

Microsoft Academic Search

We studied the distribution of laminin ?2 chain in the skeletal muscle basement membrane of 16 patients with congenital muscular dystrophy (CMD) by immunohistochemistry. A dramatic reduction in the laminin ?2 staining was observed in four patients with classical merosin-negative CMD. A moderate reduction of laminin ?2 labelling was observed in four patients with partial merosin deficiency and two patients

Ronald D. Cohn; Ralf Herrmann; Ulla M. Wewer; Thomas Voit

1997-01-01

185

Oculopharyngeal muscular dystrophy - an under-diagnosed disorder?  

Microsoft Academic Search

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant muscle disorder, usually of late onset. OPMD is among the few triplet re- peat diseases\\/ polyalanine (poly(A)) expansion dis- eases for which the function of the mutated gene is quite well established. The disease is charac- terised by slowly progressive bilateral ptosis, dys- phagia and proximal limb weakness, appearing after the age

Stephan Rüegg; Monique Lehky Hagen; Ursula Hohla; Ludwig Kappos; Peter Fuhr; Martina Plasilova; Hansjakob Müller; Karl Heinimann

186

Usefulness of myocardial strain imaging in Duchenne muscular dystrophy  

Microsoft Academic Search

Duchenne muscular dystrophy is an X-linked recessive disorder caused by the absence of dystrophin. Heart involvement is a classical complication in this disease and leads progressively to heart failure. Detecting latent myocardial involvement is essential in this disease because early use of drugs like angiotensin - converting enzyme inhibitors may delay the progression of heart disease. Myocardial strain imaging is

A. Fayssoil

2010-01-01

187

Atypical form of X-linked proximal pseudohypertrophic muscular dystrophy  

Microsoft Academic Search

A series of 95 families, consisting of 317 patients with severe and mild X-linked proximal pseudohypertrophic muscular dystrophy (MD), was analysed by the use of two different and rigid clinical criteria based on the age when the patient became chairbound. Using these criteria the families from Erfurt and Warsaw could be clearly separated into classical Duchenne (DMD) and classical Becker

A. W. J. Spiegler; I. Hausmanowa-Petrusewicz; J. Borkowska; F. H. Herrmann

1987-01-01

188

Myocardial strain changes in Duchenne muscular dystrophy without overt cardiomyopathy  

Microsoft Academic Search

BackgroundPatients with Duchenne muscular dystrophy (DMD) are at risk of the development of dilated cardiomyopathy and heart failure, thus making early identification of high-risk patients necessary. Myocardial strain imaging (MSI) can be used for quantitative analysis of wall motion of the left ventricle (LV). The aim of this study was to determine whether MSI could detect early changes in myocardial

Hitoko Ogata; Satoshi Nakatani; Yuka Ishikawa; Akifumi Negishi; Michiko Kobayashi; Yukitoshi Ishikawa; Ryoji Minami

2007-01-01

189

Becker muscular dystrophy: correlation of deletion type with clinical severity  

Microsoft Academic Search

Molecular deletion screening with cDNA probes from the dystrophin gene was undertaken in patients with Becker muscular dystrophy from 58 separate families. Deletions were found in 41 (71%) of these families. Thirty-four (83%) of the deletions started in the same intron near the centre of the gene, and although there was no precise correlation between clinical severity and deletion pattern,

A M Norman; N S Thomas; H M Kingston; P S Harper

1990-01-01

190

Preferential deletion of exons in Duchenne and Becker muscular dystrophies  

Microsoft Academic Search

Duchenne and Becker muscular dystrophy (DMD and BMD) genes are located in Xp21 on the short arm of the X chromosome. DMD patients display a much more severe clinical course than BMD patients, and yet about 10% of cases of each have been reported to have deletions for parts of the gene. Using a complementary DNA subclone of the DMD

S. M. Forrest; G. S. Cross; A. Speer; D. Gardner-Medwin; J. Burn; K. E. Davies

1987-01-01

191

The clinical, genetic and dystrophin characteristics of Becker muscular dystrophy  

Microsoft Academic Search

We have correlated a detailed clinical assessment of 67 patients with proven Becker muscular dystrophy with the results from genetic and protein analyses. There was an overall deletion frequency of 80%, rising to 92.6% in the large group of patients defined on clinical grounds as being of “typically” mild severity. The deletions in this group were all clustered in the

K. M. D. Bushby; D. Gardner-Medwin; L. V. B. Nicholson; M. A. Johnson; I. D. Haggerty; N. J. Cleghorn; J. B. Harris; S. S. Bhattacharyal

1993-01-01

192

Therapies in Muscular Dystrophy: Current Concepts and Future Prospects  

Microsoft Academic Search

In the fast moving field of muscular dystrophy, therapeutic matters are now high on the agenda. Despite little progress made in the understanding of the exact pathogenesis, hopes have been raised with the advent of molecular medicine applied to such disorders. A constellation of techniques or therapeutic solutions are now available, but very few have reached the clinical stage. Gene

J. Andoni Urtizberea

2000-01-01

193

Intellectual functioning in Duchenne muscular dystrophy: A review  

Microsoft Academic Search

Duchenne muscular dystrophy has traditionally been thought to be a primary disease of muscle, but recently it has been suggested that it may be secondary to a neuronal defect or to a generalized disorder of protein synthesis and membrane. However, to date there is no proof to support unequivocally any of these theories. A higher incidence of mental retardation and

Nicholas J. Karagan

1979-01-01

194

Phonological Awareness Skills in Young Boys with Duchenne Muscular Dystrophy  

ERIC Educational Resources Information Center

|Substantial research has detailed the reading deficits experienced by children with Duchenne muscular dystrophy (DMD). Although phonological awareness (PA) is vital in reading development, little is known about PA in the DMD population. This pilot study describes the PA abilities of a group of five young children with DMD, comparing the results…

Waring, Phoebe; Woodyatt, Gail

2011-01-01

195

The Assessment of Intelligence in Boys with Duchenne Muscular Dystrophy.  

ERIC Educational Resources Information Center

|Challenges assumptions and research procedures leading to the position that below-average intellectual potential is an integral part of Duchenne muscular dystrophy. A study of 58 boys (ages 5 to 18) from urban, suburban, and rural settings indicated IQ range of 59 to 131 and no evidence of significant verbal deficit (reported in earlier studies).…

Mearig, Judith S.

1979-01-01

196

Structural changes in the early stages of Duchenne muscular dystrophy  

Microsoft Academic Search

The finding of a relative absence of degeneration and regeneration in a muscle biopsy taken at 2½ weeks of age from a boy who later showed the florid pathological changes of preclinical Duchenne muscular dystrophy prompted a review of muscle biopsies taken from boys in the preclinical and early clinical stages of this disease. Only one other biopsy obtained in

W. G. Bradley; P. Hudgson; P. F. Larson; T. A. Papapetropoulos; M. Jenkison

1972-01-01

197

Daytime Predictors of Sleep Hypoventilation in Duchenne Muscular Dystrophy  

Microsoft Academic Search

Sleep hypoventilation is an inevitable consequence of Duchenne muscular dystrophy (DMD), usually preceding daytime respiratory failure. Appropriate scheduling of polysomnography and the intro- duction of noninvasive ventilation (NIV) during sleep are not defined. Our aim was to determine the parameters of daytime lung function associated with sleep hypoventilation in patients with DMD. As our method we chose a prospective comparison

CRAIG A. HUKINS; DAVID R. HILLMAN

198

Skeletal, cardiac, and smooth muscle failure in Duchenne muscular dystrophy  

Microsoft Academic Search

The goals of this study were to describe the clinical course of skeletal, cardiac, and gastrointestinal muscle manifestations and trends in age at diagnosis and survival of Duchenne muscular dystrophy (DMD) patients. A retrospective cohort of 33 male patients with DMD, born between 1953 and 1983 and followed at the Mayo Clinic during their second decade of life, was studied.

Benoit J. Boland; Peter L. Silbert; Robert V. Groover; Peter C. Wollan; Marc D. Silverstein

1996-01-01

199

Therapeutics for Duchenne muscular dystrophy: current approaches and future directions  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD) is the most common X-linked neuromuscular disorder. The devastating nature of DMD has led to an intense effort toward finding a cure for this disease, dating back to the time when Duchenne first initiated clinical trials using faradic stimulation for DMD patients. Unfortunately despite the passage of some 150 years the disease remains incurable, and its medical

Sasha Bogdanovich; Kelly J. Perkins; Thomas O. B. Krag; Tejvir S. Khurana

2004-01-01

200

Occupational Potential in a Population with Duchenne Muscular Dystrophy.  

ERIC Educational Resources Information Center

|Twenty-five males with Duchenne muscular dystrophy were tested to assess their potential for occupational activity. Tests measured possible sensory deficits, strength, endurance, and fatigue in response to sustained fine motor activity. Results indicate that, within limitations, persons with this diagnosis can engage in activity leading to skill…

Schkade, Janette K.; And Others

1987-01-01

201

Duchenne muscular dystrophy in one of monozygotic twin girls  

Microsoft Academic Search

Monozygotic twin girls are reported, one of whom has the typical clinical features of Duchenne muscular dystrophy despite a normal female karyotype. Although certain features of the biopsy were atypical, the clinical diagnosis was supported by persistent markedly raised blood creatine kinase levels and findings typical of DMD on electromyography and magnetic resonance spectroscopy. Analysis of an X linked DNA

J Burn; S Povey; Y Boyd; E A Munro; K Harper; D Thomas

1986-01-01

202

Poor Facial Affect Recognition among Boys with Duchenne Muscular Dystrophy  

ERIC Educational Resources Information Center

|Children with Duchenne or Becker muscular dystrophy (MD) have delayed language and poor social skills and some meet criteria for Pervasive Developmental Disorder, yet they are identified by molecular, rather than behavioral, characteristics. To determine whether comprehension of facial affect is compromised in boys with MD, children were given a…

Hinton, V. J.; Fee, R. J.; De Vivo, D. C.; Goldstein, E.

2007-01-01

203

Molecular bases of autosomal recessive limb-girdle muscular dystrophies  

Microsoft Academic Search

Limb-girdle muscular dystrophies (LGMD) are a hetero- geneous group of genetically determined disorders with a primary or predominant involvement of the pelvic or shoulder girdle musculature. The clinical course is char- acterized by great variability, ranging from severe forms with rapid onset and progression to very mild forms allowing affected people to have fairly normal life spans and activity levels.

V. N IGRO

2003-01-01

204

Problems and potential for gene therapy in Duchenne muscular dystrophy  

Microsoft Academic Search

Hopes ran high that a cure for Duchenne muscular dystrophy (DMD) would quickly follow the discovery of dystrophin by Lou Kunkel and his group in the 1980's. Myoblast transplantation, the favoured method of gene `complementation', unfortunately did not progress beyond the experimental stage. A more sober approach to gene therapy followed using a variety of transfection or direct methods to

B. A Kakulas

1997-01-01

205

Phosphorylation of intact erythrocytes in human muscular dystrophy  

SciTech Connect

The uptake of exogenous /sup 32/Pi into the membrane proteins of intact erythrocytes was measured in 8 patients with Duchenne muscular dystrophy. No abnormalities were noted after autoradiographic analysis. This contrasts with earlier results obtained when isolated membranes were phosphorylated with gamma-(/sup 32/P)ATP, and suggests a possible reinterpretation of those experiments.

Johnson, R.M.; Nigro, M.

1986-04-01

206

X Chromosome-Linked Muscular Dystrophy (mdx) in the Mouse  

Microsoft Academic Search

An X chromosome-linked mouse mutant (gene symbol, mdx) has been found that has elevated plasma levels of muscle creatine kinase and pyruvate kinase and exhibits histological lesions characteristic of muscular dystrophy. The mutants show mild clinical symptoms and are viable and fertile. Linkage analysis with four X chromosome loci indicates that mdx maps in the Hq Bpa region of the

Grahame Bulfield; W. G. Siller; P. A. L. Wight; Karen J. Moore

1984-01-01

207

Expression of laminin subunits in congenital muscular dystrophy  

Microsoft Academic Search

The expression of laminin subunits M, A, B1 and B2 was studied immunocytochemically in 25 cases of classical congenital muscular dystrophy (CMD), 11 hypotonic infants, 20 cases of a variety of inherited and acquired neuromuscular disorders, and 11 controls. Merosin, as indicated by labelling for the M chain, was deficient in 12 (48%) of the cases of classical CMD. Seven

C. A. Sewry; J. Philpot; D. Mahony; L. A. Wilson; F. Muntoni; V. Dubowitz

1995-01-01

208

New aspects on patients affected by dysferlin deficient muscular dystrophy  

Microsoft Academic Search

Mutations in the dysferlin gene lead to limb girdle muscular dystrophy 2B, Miyoshi myopathy and distal anterior compartment myopathy. A cohort of 36 patients affected by dysferlinopathy is described, in the first UK study of clinical, genetic, pathological and biochemical data. The diagnosis was established by reduction of dysferlin in the muscle biopsy and subsequent mutational analysis of the dysferlin

Lars Klinge; Ahmed Aboumousa; Michelle Eagle; Judith Hudson; Anna Sarkozy; Gianluca Vita; Richard Charlton; Mark Roberts; Volker Straub; Rita Barresi; Hanns Lochmüller; Kate Bushby

2009-01-01

209

Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach.  

PubMed

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations in the dystrophin gene. We studied 106 patients with a diagnosis of probable DMD/BMD by analyzing 20 exons of the dystrophin gene in their blood and, in some of the cases, by immunohistochemical assays for dystrophin in muscle biopsies. In 71.7% of the patients, deletions were found in at least one of the exons; 68% of these deletions were in the hot-spot 3' region. Deletions were found in 81.5% of the DMD cases and in all the BMD cases. The cases without deletions, which included the only woman in the study with DMD, had dystrophin deficiency. The symptomatic female carriers had no deletions but had abnormal dystrophin distribution in the sarcolemma (discontinuous immunostains). The following diagnoses were made for the remaining cases without deletions with the aid of a muscle biopsy: spinal muscular atrophy, congenital myopathy; sarcoglycan deficiency and unclassified limb-girdle muscular dystrophy. Dystrophin analysis by immunohistochemistry continues to be the most specific method for diagnosis of DMD/BMD and should be used when no exon deletions are found in the dystrophin gene in the blood. PMID:17420831

Freund, Aline Andrade; Scola, Rosana Herminia; Arndt, Raquel Cristina; Lorenzoni, Paulo José; Kay, Claudia Kamoy; Werneck, Lineu Cesar

2007-03-01

210

The Childhood Muscular Dystrophies: Diseases Sharing a Common Pathogenesis of Membrane Instability  

Microsoft Academic Search

New observations demonstrate that several childhood forms of muscular dystrophy share a common pathogenesis. In muscle, dystrophin occurs as part of a membrane complex (dystrophin-glycoprotein) linking the cytoskeleton to the basal lamina. In Duchenne muscular dystrophy, dystrophin deficiency disrupts the linkage of the integral glycoproteins of the sarcolemma and leads to muscle fiber necrosis. In severe childhood autosomal recessive muscular

Jerry R. Mendell; Zarife Sahenk; Thomas W. Prior

1995-01-01

211

[Pseudohypertrophic proximal progressive muscular dystrophy with a malignant course manifesting itself in adolescence].  

PubMed

The authors describe an unique case of progressive muscular dystrophy in four brothers T. The disease was peculiar in its debut in adolescence, localization of muscular atrophies in proximal limbs, pseudohypertrophy of various muscular groups, malignant course of the myodystrophy with concomitant endocrine and metabolic disorders. A primarily muscular nature of the disease was confirmed in electrophysiological and pathological investigation. X-linked recessive inheritance of the progressive muscular dystrophy was supposed in T family. The issues of differential diagnosis, clinical polymorphism and genetical heterogeneity of X-linked recessive progressive muscular dystrophies are discussed. PMID:2728733

Badalian, L O; Temin, P A; Saidbegov, D G; Nikitin, M V; Arkhipov, B A

1989-01-01

212

Fat Embolism Syndrome following minor trauma in Duchenne muscular dystrophy.  

PubMed

We describe five patients with Duchenne muscular dystrophy who presented with acute neurologic and respiratory symptoms following minor trauma. Four of the five deteriorated rapidly and died within 36 h after falling. X-rays for fractures were negative. Four of the five patients were taking corticosteroids daily. All five patients fulfilled the clinical criteria for Fat Embolism Syndrome. Autopsy findings were consistent with fat embolism in two cases. Fat Embolism Syndrome needs to be considered in patients with Duchenne muscular dystrophy following minor trauma even without fractures. Early recognition of Fat Embolism Syndrome and aggressive resuscitation are important to improve survival. This report serves as an important reminder that seatbelts need to be used at all times. PMID:22920089

McAdam, Laura C; Rastogi, Anjali; Macleod, Kathleen; Douglas Biggar, W

2012-08-21

213

Challenges to oligonucleotides-based therapeutics for Duchenne muscular dystrophy  

PubMed Central

Antisense oligonucleotides are short nucleic acids designed to bind to specific messenger RNAs in order to modulate splicing patterns or inhibit protein translation. As such, they represent promising therapeutic tools for many disorders and have been actively developed for more than 20 years as a form of molecular medicine. Although significant progress has been made in developing these agents as drugs, they are yet not recognized as effective therapeutics and several hurdles remain to be overcome. Within the last few years, however, the prospect of successful oligonucleotides-based therapies has moved a step closer, in particular for Duchenne muscular dystrophy. Clinical trials have recently been conducted for this myopathy, where exon skipping is being used to achieve therapeutic outcomes. In this review, the recent developments and clinical trials using antisense oligonucleotides for Duchenne muscular dystrophy are discussed, with emphasis on the challenges ahead for this type of therapy, especially with regards to delivery and regulatory issues.

2011-01-01

214

Muscular dystrophy associated with beta-Dystroglycan deficiency.  

PubMed

beta-Dystroglycan, a 43-kd transmembrane dystrophin-associated glycoprotein, plays an important role in linking dystrophin to the laminin-binding alpha-dystroglycan. alpha-/beta-Dystroglycan is encoded by a single gene on chromosome 3p21 and ubiquitously expressed in muscle and nonmuscle tissues. No known human diseases have been mapped to this locus. Here, we describe the selective deficiency of beta-dystroglycan in a 4-year-old Saudi boy with muscular dystrophy. The patient had a borderline elevation of serum creatine kinase level and early-onset proximal symmetrical muscle weakness and wasting without calf hypertrophy. The milder phenotype may suggest a secondary deficiency of beta-dystroglycan; however, the unique immunofluorescence labeling suggests that the patient may present a novel form of muscular dystrophy. PMID:9007100

Salih, M A; Sunada, Y; Al-Nasser, M; Ozo, C O; Al-Turaiki, M H; Akbar, M; Campbell, K P

1996-12-01

215

A unifying genetic model for facioscapulohumeral muscular dystrophy.  

PubMed

Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy in adults that is foremost characterized by progressive wasting of muscles in the upper body. FSHD is associated with contraction of D4Z4 macrosatellite repeats on chromosome 4q35, but this contraction is pathogenic only in certain "permissive" chromosomal backgrounds. Here, we show that FSHD patients carry specific single-nucleotide polymorphisms in the chromosomal region distal to the last D4Z4 repeat. This FSHD-predisposing configuration creates a canonical polyadenylation signal for transcripts derived from DUX4, a double homeobox gene of unknown function that straddles the last repeat unit and the adjacent sequence. Transfection studies revealed that DUX4 transcripts are efficiently polyadenylated and are more stable when expressed from permissive chromosomes. These findings suggest that FSHD arises through a toxic gain of function attributable to the stabilized distal DUX4 transcript. PMID:20724583

Lemmers, Richard J L F; van der Vliet, Patrick J; Klooster, Rinse; Sacconi, Sabrina; Camaño, Pilar; Dauwerse, Johannes G; Snider, Lauren; Straasheijm, Kirsten R; van Ommen, Gert Jan; Padberg, George W; Miller, Daniel G; Tapscott, Stephen J; Tawil, Rabi; Frants, Rune R; van der Maarel, Silvère M

2010-08-19

216

Limb-Girdle Muscular Dystrophy in the United States  

Microsoft Academic Search

Limb-girdle muscular dystrophy (LGMD) has been linked to 15 chromosomal loci, 7 autosomal-dominant (LGMD1A to E) and 10 autosomal-recessive (LGMD2A to J). To determine the distribution of subtypes among patients in the United States, 6 medical centers evaluated patients with a referral diagnosis of LGMD. Muscle biopsies provided histopathology and immunodiagnostic testing, and their protein abnormalities along with clinical parameters

Steven A. Moore; Christopher J. Shilling; Steven Westra; Cheryl Wall; Matthew P. Wicklund; Catherine Stolle; Charlotte A. Brown; Daniel E. Michele; Federica Piccolo; Thomas L. Winder; Aaron Stence; Rita Barresi; Nick King; Wendy King; Julaine Florence; Kevin P. Campbell; Gerald M. Fenichel; Hansell H. Stedman; John T. Kissel; Robert C. Griggs; Shree Pandya; Katherine D. Mathews; Alan Pestronk; Carmen Serrano; Daniel Darvish; Jerry R. Mendell

2006-01-01

217

Germinal mosaicism for LMNA mimics autosomal recessive congenital muscular dystrophy  

Microsoft Academic Search

Life-threatening cardiac and respiratory complications are common in LMNA-related myopathies and early diagnosis is important for optimal patient care. Lamin A\\/C related congenital muscular dystrophy (L-CMD) is often caused by de novo mutation in LMNA, affecting a single child in a family. Germinal mosaicism is a rarer variant that can lead to two children inheriting the same new heterozygous mutation

Samira Makri; Nigel F. Clarke; Pascale Richard; Svetlana Maugenre; Laurence Demay; Gisèle Bonne; Pascale Guicheney

2009-01-01

218

Mitochondrial Abnormalities in Genetically Assessed Oculopharyngeal Muscular Dystrophy  

Microsoft Academic Search

We report a family with a clinical diagnosis of oculopharyngeal muscular dystrophy in which muscle biopsy showed mitochondrial changes such as cytochrome-c-oxidase-negative fibers and aggregates of mitochondria containing paracrystalline inclusions. Molecular analysis demonstrated a GCG expansion in the poly(A)-binding protein 2 (PABP2) gene and failed to demonstrate multiple deletions of mtDNA. We hypothesize that mitochondrial abnormalities may be a secondary

S. Gambelli; A. Malandrini; F. Ginanneschi; G. Berti; E. Cardaioli; R. De Stefano; M. Franci; C. Salvadori; F. Mari; M. Bruttini; A. Rossi; A. Federico; A. Renieri

2004-01-01

219

Disturbed Sleep in a Patient with Duchenne Muscular Dystrophy  

Microsoft Academic Search

17-year-old white male with Duchenne muscular dystrophy presented to the pediatric pulmonary clinic for a follow-up evaluation after being hospitalized for pneumonia. During the hospital stay he was noted to have nocturnal desaturation inter- mittently during sleep. The patient has been wheelchair bound since age 12 years. His father's two current concerns include the patient's difficulty swallowing and difficulty breathing

Mary H. Wagner; Richard B. Berry

220

Late gadolinium enhancement: precursor to cardiomyopathy in Duchenne muscular dystrophy?  

Microsoft Academic Search

Background Progressive cardiomyopathy is a common cause of death in Duchenne muscular dystrophy (DMD), presumably secondary to fibrosis\\u000a of the myocardium. The posterobasal and left lateral free wall of the left ventricle (LV) are initial sites of myocardial\\u000a fibrosis pathologically. The purposes of this study were to assess whether cardiac magnetic resonance imaging (CMRI), utilizing\\u000a late gadolinium enhancement (LGE), could

Michael D. Puchalski; Richard V. Williams; Bojana Askovich; C. Todd Sower; Kan H. Hor; Jason T. Su; Nathan Pack; Edward Dibella; William M. Gottliebson

2009-01-01

221

Genetic heterogeneity in 30 German patients with oculopharyngeal muscular dystrophy  

Microsoft Academic Search

Oculopharyngeal muscular dystrophy (OPMD) is due to short elongations of a polyalanine tract in the poly(A) binding protein\\u000a nuclear 1 (PABPN1) gene. Originally GCG expansions in which (GCG)6 is extended to (GCG)7–13 were found. Subsequently five further genotypes with additional GCA– and GCG–trinucleotides were identified in single OPMD\\u000a patients. This indicated larger genetic heterogeneity and showed that unequal crossing–over and

T. Müller; M. Deschauer; F. Kolbe-Fehr

2006-01-01

222

Facioscapulohumeral muscular dystrophy in mice overexpressing FRG1  

Microsoft Academic Search

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder that is not due to a classical mutation within a protein-coding gene. Instead, almost all FSHD patients carry deletions of an integral number of tandem 3.3-kilobase repeat units, termed D4Z4, located on chromosome 4q35 (ref. 3). D4Z4 contains a transcriptional silencer whose deletion leads to inappropriate overexpression in FSHD skeletal

Davide Gabellini; Giuseppe D'Antona; Maurizio Moggio; Alessandro Prelle; Chiara Zecca; Raffaella Adami; Barbara Angeletti; Patrizia Ciscato; Maria Antonietta Pellegrino; Roberto Bottinelli; Michael R. Green; Rossella Tupler

2006-01-01

223

Cardiomyopathy in Duchenne muscular dystrophy: pathogenesis and therapeutics  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by the absence of dystrophin, a sarcolemmal protein\\u000a which links the cytoskeleton to the extracellular matrix by interacting with a large number of proteins. Heart failure is\\u000a a classic complication of this disease. The authors review the pathogenesis and therapeutics of cardiac involvement in DMD.

Abdallah Fayssoil; Olivier Nardi; David Orlikowski; Djillali Annane

2010-01-01

224

Early Observations on Duchenne-Meryon Muscular Dystrophy  

Microsoft Academic Search

Duchenne muscular dystrophy is an X-linked recessive, progressive muscle-wasting disease affecting all world populations equally, with an incidence of about 1 in every 5,000 live male births. Duchenne made use of his invention, the ‘harpoon’ that he employed to perform percutaneous muscle biopsies; not surprisingly, this aroused hostile criticism of its ethical propriety, in the local press. The discovery of

J. M. S. Pearce

2005-01-01

225

Succinylcholine-induced cardiac arrest in unsuspected Duchenne muscular dystrophy  

Microsoft Academic Search

A case history is presented of a three-year-old boy with unsuspected Duchenne muscular dystrophy, who suffered a cardiac arrest\\u000a following the administration of a single dose of succinylcholine during a halothane anaesthetic. The arrest was associated\\u000a with lack of fasciculations, muscle rigidity, hyperkalemia, myoglobinuria, and massive elevation of serum creatine phosphokinase.\\u000a Asystole was prolonged and refractory to treatment, although cardiac

W. A. V. Henderson

1984-01-01

226

Progress in gene therapy for Duchenne muscular dystrophy  

Microsoft Academic Search

Gene transfer research for Duchenne muscular dystrophy (DMD) has brought the goal of successful treatment of this devastating,\\u000a inherited disease closer to being a reality. Although gene therapeutic approaches for DMD patients are not yet in clinical\\u000a use, recent advances using DMD animal models are encouraging. Progress in vector design, such as high-capacity adenoviral\\u000a vectors, targeted adenoviral vectors, and heterodimerization

Paula R. Clemens; F Jason Duncan

2001-01-01

227

Deletion patterns of Duchenne and Becker muscular dystrophies in Greece  

Microsoft Academic Search

We present molecular data from 90 Greek boys with Duchenne or Becker muscular dystrophy using cDNA analysis or multiplex PCR or both. Deletions were detected in 63.3% of patients and were mainly clustered in two areas of the gene, one in the 3' and one in the 5' end of the gene (exons 3-19 and 44-53). Almost 17% of deletion

L Florentin; A Mavrou; K Kekou; C Metaxotou

1995-01-01

228

Patterns of exon deletions in Duchenne and Becker muscular dystrophy  

Microsoft Academic Search

A panel of patients with Duchenne and Becker muscular dystrophy (DMD and BMD) has been screened with the cDNA probes Cf56a and Cf23a, which detect exons in the central part of the DMD gene. One or more exons were deleted in 60% of patients. The deletions were mapped and prove to be heterogeneous in size and extent, particularly in DMD.

A. P. Read; R. C. Mountford; S. M. Forrest; S. J. Kenwrick; K. E. Davies; R. Harris

1988-01-01

229

Elderly Onset of Weakness in Facioscapulohumeral Muscular Dystrophy  

PubMed Central

A 77-year-old male is presented. He had onset of proximal weakness 10 years earlier. His course was slowly progressive. Despite having phenotypic features of facioscapulohumeral muscular dystrophy (FSH), genetic testing for this was delayed because of his age of onset, lack of family history, and benign appearing muscle biopsy. This case is one of the oldest onset of weakness in genetically confirmed FSH and highlights the recognized expansion in phenotype that has occurred since the advent of genetic testing.

Fee, Dominic B.

2012-01-01

230

Cardiac and respiratory involvement in advanced stage Duchenne muscular dystrophy  

Microsoft Academic Search

This study aimed to describe myocardial involvement, respiratory impairment and pulmonary blood flow abnormalities in advanced-stage Duchenne muscular dystrophy (DMD). Twenty-one wheelchair-bound patients, aged from 10 to 24 yr, underwent electrocardiographic and echocardiographic examination, conventional spirometry, diurnal arterial blood gas analysis, and nocturnal polysomnography (SaO2 monitoring). Diagnosis was confirmed by neurological examination, dystrophin analysis at protein and DNA level. Patients

P. Melacini; A. Vianello; C. Villanova; M. Fanin; M. Miorin; C. Angelini; S. Dalla Volta

1996-01-01

231

Duchenne muscular dystrophy quantification: a multivariate analysis of surface EMG  

Microsoft Academic Search

The paper describes a method of quantifying Duchenne muscular dystrophy which is examiner independent and uses surface electromyographic\\u000a signals (EMG). A standardised protocol is proposed. Spectral parameters are first computed from digitised EMG, then a polynomial\\u000a model is deduced from the evolution of each parameter. A discriminant analysis between healthy and DMD subjects leads to the\\u000a determination of a discriminant

A. Priez; J. Duchene; F. Goubel

1992-01-01

232

The role of defective glycosylation in congenital muscular dystrophy  

Microsoft Academic Search

The dystrophin glycoprotein complex (DGC) is an assembly of proteins spanning the sarcolemma of skeletal muscle cells. Defects\\u000a in the DGC appear to play critical roles in several muscular dystrophies due to disruption of basement membrane organization.\\u000a O-mannosyl oligosaccharides on ?-dystroglycan, a major extracellular component of the DGC, are essential for normal binding\\u000a of ?-dystroglycan to ligands (such as laminin)

Harry Schachter; Jiri Vajsar; Wenli Zhang

2003-01-01

233

Malignant hyperpyrexia and duchenne muscular dystrophy: A case report  

Microsoft Academic Search

We report a patient with Duchenne muscular dystrophy who developed malignant hyperpyrexia during general anaesthesia. During\\u000a anaesthesia bradycardia was followed by ventricular fibrillation, on which ventricular flutter supervened and a body temperature\\u000a rise of 0.6°C for 15 minutes, myoglobinuria and elevation of CPK level were observed. The caffeine sensitivity test of biopsied\\u000a muscle fibers revealed an increase in sensitivity, although

Shigehiro Oka; Yoshio Igarashi; Akio Takagi; Mitsuhiro Nishida; Kazuo Sato; Kazumasa Nakada; Kazuyuki Ikeda

1982-01-01

234

A cDNA clone from the Duchenne\\/Becker muscular dystrophy gene  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD) is the most common of the muscular dystrophies affecting one in 3,000 live male births (see refs 1, 2 for review). Both DMD and the mild form, Becker muscular dystrophy (BMD), are X-linked. There are a number of females affected by the disease who all possess an X-autosome translocation, with the exchange point in the X

Arthur H. M. Burghes; Cairine Logan; Xiuyuan Hu; Bonnie Belfall; Ronald G. Worton; Peter N. Ray

1987-01-01

235

Limb–Girdle and Congenital Muscular Dystrophies: Current Diagnostics, Management, and Emerging Technologies  

Microsoft Academic Search

The muscular dystrophies show muscle degeneration and regeneration (necrotizing myopathy) on muscle biopsy, typically associated\\u000a with elevated serum creatine kinase, and muscle weakness. In 1986, the first causative gene was identified for the most prevalent\\u000a and best-characterized form of muscular dystrophy, Duchenne muscular dystrophy. Over the past 25 years, the number of other\\u000a genes determined to cause different subtypes has grown

Carolina Tesi Rocha; Eric P. Hoffman

2010-01-01

236

A small deletion in the Duchenne\\/Becker muscular dystrophy locus —a functionally important region?  

Microsoft Academic Search

A DNA deletion in a patient with Becker muscular dystrophy (BMD) has been delineated by restriction endonuclease mapping. The deletion is unusually small, removing six kilobases (kb) of DNA distal to pERT 87-1 (DXS164). This region has previously been shown to contain an exon of a candidate gene which, when defective, causes Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy.

K. A. Hart; A. P. Monaco; L. M. Kunkel; M. Bobrow

1987-01-01

237

Targeted exon skipping as a potential gene correction therapy for Duchenne muscular dystrophy  

Microsoft Academic Search

Duchenne muscular dystrophy is primarily caused by frame-disrupting mutations in the Duchenne muscular dystrophy gene which abort dystrophin synthesis. We have explored a gene correction therapy aimed at restoration of the reading frame in Duchenne muscular dystrophy patients. Through the binding of antisense oligoribonucleotides to exon-internal sequences in the pre-mRNA, the splicing can be manipulated in such a manner that

Annemieke Aartsma-Rus; Mattie Bremmer-Bout; Anneke A. M Janson; Johan T den Dunnen; Gert-Jan B van Ommen; Judith C. T van Deutekom

2002-01-01

238

A phase I\\/IItrial of MYO029 in adult subjects with muscular dystrophy  

Microsoft Academic Search

Objective: Myostatin is an endogenous negative regulator of muscle growth and a novel target for muscle diseases. We con- ducted a safety trial of a neutralizing antibody to myostatin, MYO-029, in adult muscular dystrophies (Becker muscular dys- trophy, facioscapulohumeral dystrophy, and limb-girdle muscular dystrophy). Methods: This double-blind, placebo-controlled, multinational, randomized study included 116 subjects divided into sequential dose-escalation cohorts, each

Kathryn R. Wagner; James L. Fleckenstein; Anthony A. Amato; Richard J. Barohn; Katharine Bushby; Diana M. Escolar; Kevin M. Flanigan; Alan Pestronk; Rabi Tawil; Gil I. Wolfe; Michelle Eagle; Julaine M. Florence; Wendy M. King; Shree Pandya; Volker Straub; Paul Juneau; Kathleen Meyers; Cristina Csimma; Tracey Araujo; Robert Allen; Stephanie A. Parsons; John M. Wozney; Edward R. LaVallie; Jerry R. Mendell

2008-01-01

239

Lung and respiratory muscle function in limb girdle muscular dystrophy.  

PubMed Central

BACKGROUND--Pulmonary involvement is frequently observed in patients with limb girdle muscular dystrophy and occurs early in the disease. The aim of this study was to establish the prevalence of pulmonary dysfunction; the type of dysfunction; and any correlation between patient age, disease duration, or limb weakness and lung or respiratory muscle dysfunction. METHODS--Twenty patients with strictly delineated limb girdle muscular dystrophy and 20 healthy controls were evaluated. Full inspiration chest radiographs were obtained. Standard lung and respiratory muscle function tests were performed and the data were statistically analysed. RESULTS--The mean age of the patients was 40.6 years, the mean disease duration was 18.9 years, and the mean average muscle score (a numerical expression of limb weakness) was 5.73 out of 10. Chest radiography showed unilateral paresis of the diaphragm in three patients. Increased residual volumes, with either increased or decreased total lung capacity, correlated inversely with disease duration. Respiratory muscle weakness was common but mild. Expiratory muscle function was more impaired than inspiratory muscle function and correlated positively with expiratory reserve volume. CONCLUSIONS--Respiratory muscle strength is commonly impaired in limb girdle muscle dystrophy. A dissociation of the limb and mild respiratory muscle involvement is observed; wheelchair restriction does not predict worsening of pulmonary function, and patient age, disease duration, or degree of limb weakness do not predict pulmonary morbidity. The diaphragm is not disproportionately affected by the dystrophic process compared with limb muscles.

Stubgen, J P; Ras, G J; Schultz, C M; Crowther, G

1994-01-01

240

Stem cell therapies to treat muscular dystrophy: progress to date.  

PubMed

Muscular dystrophies are heritable, heterogeneous neuromuscular disorders and include Duchenne and Becker muscular dystrophies (DMD and BMD, respectively). DMD patients exhibit progressive muscle weakness and atrophy followed by exhaustion of muscular regenerative capacity, fibrosis, and eventually disruption of the muscle tissue architecture. In-frame mutations in the dystrophin gene lead to expression of a partially functional protein, resulting in the milder BMD. No effective therapies are available at present. Cell-based therapies have been attempted in an effort to promote muscle regeneration, with the hope that the host cells would repopulate the muscle and improve muscle function and pathology. Injection of adult myoblasts has led to the development of new muscle fibers, but several limitations have been identified, such as poor cell survival and limited migratory ability. As an alternative to myoblasts, stem cells were considered preferable for therapeutic applications because of their capacity for self-renewal and differentiation potential. In recent years, encouraging results have been obtained with adult stem cells to treat human diseases such as leukemia, Parkinson's disease, stroke, and muscular dystrophies. Embryonic stem cells (ESCs) can be derived from mammalian embryos in the blastocyst stage, and because they can differentiate into a wide range of specialized cells, they hold potential for use in treating almost all human diseases. Several ongoing studies focus on this possibility, evaluating differentiation of specific cell lines from human ESCs (hESCs) as well as the potential tumorigenicity of hESCs. The most important limitation with using hESCs is that it requires destruction of human blastocysts or embryos. Conversely, adult stem cells have been identified in various tissues, where they serve to maintain, generate, and replace terminally differentiated cells within their specific tissue as the need arises for cell turnover or from tissue injury. Moreover, these cells can participate in regeneration of more than just their specific tissue type. Here we describe multiple types of muscle- and fetal-derived myogenic stem cells, their characterization, and their possible use in treating muscular dystrophies such as DMD and BMD. We also emphasize that the most promising possibility for the management and therapy of DMD and BMD is a combination of different approaches, such as gene and stem cell therapy. PMID:20623990

Meregalli, Mirella; Farini, Andrea; Parolini, Daniele; Maciotta, Simona; Torrente, Yvan

2010-08-01

241

Congenital Muscular Dystrophy With Complete Laminin-?2Deficiency, Cortical Dysplasia, and Cerebral White-Matter Changes in Children  

Microsoft Academic Search

Congenital muscular dystrophy consists of Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, muscle-eye-brain disease, and occidental congenital muscular dystrophy, which is further divided into laminin-?2-positive and laminin-?2-negative subgroups. These forms of congenital muscular dystrophy are frequently associated with abnormal white-matter changes, whereas the Fukuyama form, Walker-Warburg syndrome, and muscle-eye-brain disease are also frequently found to have polymicrogyria. We now report two

Chang-Yong Tsao; Jerry R. Mendell; Jerome Rusin; Mark Luquette

1998-01-01

242

Congenital muscular dystrophy with adducted thumbs, ptosis, external ophthalmoplegia, mental retardation and cerebellar hypoplasia: a novel form of CMD  

Microsoft Academic Search

At least six different forms of congenital muscular dystrophy are associated with structural changes of the central nervous system, and three of these have been mapped: merosin-deficient congenital muscular dystrophy on chromosome 6q2, Fukuyama congenital muscular dystrophy on chromosome 9q31, and muscle eye brain disease on chromosome 1p32. Walker-Warburg syndrome, congenital muscular dystrophy with calf hypertrophy, pontocerebellar hypoplasia, and normal

Th Voit; E Parano; V Straub; J. M Schröder; J Schaper; P Pavone; R Falsaperla; L Pavone; R Herrmann

2002-01-01

243

Identification of three distinguishable phenotypes in golden retriever muscular dystrophy.  

PubMed

Duchenne muscular dystrophy (DMD) is a human disease characterized by progressive and irreversible skeletal muscle degeneration caused by mutations in genes coding for important muscle proteins. Unfortunately, there is no efficient treatment for this disease; it causes progressive loss of motor and muscular ability until death. The canine model (golden retriever muscular dystrophy) is similar to DMD, showing similar clinical signs. Fifteen dogs were followed from birth and closely observed for clinical signs. Dogs had their disease status confirmed by polymerase chain reaction analysis and genotyping. Clinical observations of musculoskeletal, morphological, gastrointestinal, respiratory, cardiovascular, and renal features allowed us to identify three distinguishable phenotypes in dystrophic dogs: mild (grade I), moderate (grade II) and severe (grade III). These three groups showed no difference in dystrophic alterations of muscle morphology and creatine kinase levels. This information will be useful for therapeutic trials, because DMD also shows significant, inter- and intra-familiar clinical variability. Additionally, being aware of phenotypic differences in this animal model is essential for correct interpretation and understanding of results obtained in pre-clinical trials. PMID:19440974

Ambrósio, C E; Fadel, L; Gaiad, T P; Martins, D S; Araújo, K P C; Zucconi, E; Brolio, M P; Giglio, R F; Morini, A C; Jazedje, T; Froes, T R; Feitosa, M L T; Valadares, M C; Beltrão-Braga, P C B; Meirelles, F V; Miglino, M A

2009-04-07

244

The limb-girdle muscular dystrophies--multiple genes,multiple mechanisms  

Microsoft Academic Search

In the field of muscular dystrophy, advances in understanding the molecular basis of the various disorders in this group have been rapidly translated into readily applicable diagnostic tests, allowing the provision of more accurate prognostic and genetic counselling. The limb-girdle muscular dystrophies (LGMD) have recently undergone a major reclassification according to their genetic basis. Currently 13 different types can be

Katharine M. D. Bushby

1999-01-01

245

Myocardial Delayed Enhancement by Magnetic Resonance Imaging in Patients With Muscular Dystrophy  

Microsoft Academic Search

Objectives This study sought to analyze whether cardiovascular magnetic resonance (CMR) can detect and quantify myocar- dial damage in the early stages of cardiomyopathy in muscular dystrophies (MD). Background Muscular dystrophy is a genetic disease that involves skeletal and cardiac tissues of humans. Cardiomyopathy is common, and death secondary to cardiac or respiratory diseases occurs early in life. Cardiovascular magnetic

Marly Conceição Silva; Zilda Maria Alves Meira; Juliana Gurgel Giannetti; Marcelo Moreira da Silva; Alysson Félix Oliveira Campos; Márcia de Melo Barbosa; Geraldo Moll; Starling Filho; Rogério de Aguiar Ferreira; Mayana Zatz; Carlos Eduardo Rochitte

2007-01-01

246

Cryptic splicing involving the splice site mutation in the canine model of Duchenne muscular dystrophy  

Microsoft Academic Search

Golden retriever muscular dystrophy arises from a mutation in the acceptor splice site of intron 6 of the dystrophin gene. Skipping of exon 7 disrupts the mRNA reading frame and results in premature termination of translation. We are using this animal model to evaluate treatments for Duchenne muscular dystrophy, including gene repair induced by chimeric oligonucleotides. After injection of golden

S. Fletcher; T. Ly; R. M. Duff; J. McC Howell; S. D. Wilton

2001-01-01

247

Introduction of genes relating to muscular dystrophy into chimeric chickens by embryo engineering  

Microsoft Academic Search

A novel system has been developed to introduce genes relating to muscular dystrophy to chimeric chickens. Fertilized eggs were obtained from New Hampshire chicken; NH-413 strain which have genes relating to Fukuyama type muscular dystrophy. Blastoderms were isolated from these embryos. Cells from the center of area pellucida were specifically isolated from the blastoderms. Excess yolk were removed by PBS

Akira Fujiwara; Makoto Mizutani; Tamao Ono; Hiroshi Kagami

248

The molecular basis of activity-induced muscle injury in Duchenne muscular dystrophy  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD) is the most common of the human muscular dystrophies, affecting approximately 1 in 3500 boys. Most DMD patients die in their late teens or early twenties due to involvement of the diaphragm and other respiratory muscles by the disease. The primary abnormality in DMD is an absence of dystrophin, a 427 kd protein normally found at

Basil J. Petrof

1998-01-01

249

Severe visual loss associated with retinal telangiectasis and facioscapulohumeral muscular dystrophy  

Microsoft Academic Search

Facioscapulohumeral (FSH) muscular dystrophy is known to be associated with retinal telangiectasis. However, there are only few reports of severe visual loss due to exudative complications, so the risk to vision has not been established. Because of the possible therapeutic implications, we have described two cases of young girls who developed FSH muscular dystrophy and exudative retinal detachment due to

Daniel Pauleikhoff; Norbert Bornfeld; Alan C. Bird; Achim Wessing

1992-01-01

250

Limb–girdle muscular dystrophy: Diagnostic evaluation, frequency and clues to pathogenesis  

Microsoft Academic Search

We characterized the frequency of limb–girdle muscular dystrophy (LGMD) subtypes in a cohort of 76 Australian muscular dystrophy patients using protein and DNA sequence analysis. Calpainopathies (8%) and dysferlinopathies (5%) are the most common causes of LGMD in Australia. In contrast to European populations, cases of LGMD2I (due to mutations in FKRP) are rare in Australasia (3%). We have identified

Harriet P. Lo; Sandra T. Cooper; Frances J. Evesson; Jane T. Seto; Maria Chiotis; Valerie Tay; Alison G. Compton; Anita G. Cairns; Alistair Corbett; Daniel G. MacArthur; Nan Yang; Katrina Reardon; Kathryn N. North

2008-01-01

251

Living with muscular dystrophy: health related quality of life consequences for children and adults  

Microsoft Academic Search

BACKGROUND: Muscular dystrophies are chronic diseases manifesting with progressive muscle weakness leading to decreasing activities and participation. To understand the impact on daily life, it is important to determine patients' quality of life. OBJECTIVE: To investigate Health Related Quality of Life (HRQoL) of children and adults with muscular dystrophy (MD), and to study the influence of type and severity of

Martha A Grootenhuis; Judith de Boone; Anneke J van der Kooi

2007-01-01

252

Visual Function in Children With Merosin-Deficient and Merosin-Positive Congenital Muscular Dystrophy  

Microsoft Academic Search

This study evaluates whether abnormalities of visual function are present in children with congenital muscular dystrophy and whether these, if present, are associated with merosin status or magnetic resonance imaging (MRI) findings. Twenty children (age range 5-17 years) with a diagnosis of classical congenital muscular dystrophy were assessed on visual acuity, stereopsis, and visual fields and the results compared with

Eugenio Mercuri; Shirley Anker; Joanne Philpot; Caroline Sewry; Victor Dubowitz; Francesco Muntoni

1998-01-01

253

Altered aquaporin-4 expression in human muscular dystrophies: a common feature?  

Microsoft Academic Search

Duchenne Muscular Dystrophy (DMD) is a progressive lethal muscle disease that affects young boys. Dystrophin, absent in DMD and reduced in the milder form Becker Muscular Dystrophy (BMD), binds to several membrane-associated proteins known as dystrophin-associated proteins (DAPs). Once this critical structural link is disrupted, muscle fibers become more vulnerable to mechanical and osmotic stress. Recently, we have reported that

Antonio Frigeri; Grazia Paola Nicchia; Silvia Repetto; Massimo Bado; Carlo Minetti; Maria Svelto

2002-01-01

254

Abnormalities of dystrophin, the sarcoglycans, and laminin alpha2 in the muscular dystrophies  

Microsoft Academic Search

Abnormalities of dystrophin, the sarcoglycans, and laminin alpha2 are responsible for a subset of the muscular dystrophies. In this study we aim to characterise the nature and frequency of abnormalities of these proteins in an Australian population and to formulate an investigative algorithm to aid in approaching the diagnosis of the muscular dystrophies. To reduce ascertainment bias, biopsies with dystrophic

K J Jones; S S Kim; K N North

1998-01-01

255

A novel FKRP mutation in congenital muscular dystrophy disrupts the dystrophin glycoprotein complex  

Microsoft Academic Search

Mutations in the gene encoding fukutin related protein (FKRP) produce a spectrum of disease including congenital muscular dystrophy and limb girdle muscular dystrophy. FKRP is one member of a class of molecules thought to be glycosyltransferases that mediate O-linked glycosylation. The primary target of these glycosyltransferases is thought to be dystroglycan. We now report two unrelated Mexican children with congenital

Heather MacLeod; Peter Pytel; Robert Wollmann; Ewa Chelmicka-Schorr; Kenneth Silver; Rebecca Brown Anderson; Darrel Waggoner; Elizabeth M. McNally

2007-01-01

256

Muscle magnetic resonance imaging in patients with congenital muscular dystrophy and Ullrich phenotype  

Microsoft Academic Search

The aim of this study was to evaluate muscle magnetic resonance imaging findings in patients with congenital muscular dystrophy and Ullrich phenotype. Fifteen children with congenital muscular dystrophy and Ullrich phenotype were included in the study. All patients had collagen VI studies in muscle and, when family structure was informative, linkage studies to the collagen 6 loci. Three of the

E Mercuri; C Cini; A Pichiecchio; J Allsop; S Counsell; Z Zolkipli; S Messina; M Kinali; S. C Brown; C Jimenez; M Brockington; Y Yuva; C. A Sewry; F Muntoni

2003-01-01

257

Evidence of left ventricular dysfunction in children with merosin-deficient congenital muscular dystrophy  

Microsoft Academic Search

Background Deficiency of the sarcolemmal protein dystrophin has been linked to dilated cardiomyopathy. Some children with congenital muscular dystrophy have a deficiency of the laminin ?2 chain of merosin, an extracellular matrix protein linked to dystrophin through a group of glycoproteins. It has been shown that deficiency in one of these glycoproteins is responsible for muscular dystrophy and dilated cardiomyopathy.

Nicos Spyrou; Jo Philpot; Rodney Foale; Paolo G. Camici; Francesco Muntoni

1998-01-01

258

Familial concordance of brain magnetic resonance imaging changes in congenital muscular dystrophy  

Microsoft Academic Search

Cerebral white matter changes have been described in a significant number of individual patients with “pure” congenital muscular dystrophy without clinical evidence of central nervous system involvement. The cause for the imaging changes is unknown but it is possible that they are the result of abnormal expression in the brain of the gene also responsible for the muscular dystrophy. In

J. Philpot; H. Topaloglu; J. Pennock; V. Dubowitz

1995-01-01

259

Muscular dystrophy associated with ?-dystroglycan deficiency in Sphynx and Devon Rex cats  

Microsoft Academic Search

Recent studies have identified a number of forms of muscular dystrophy, termed dystroglycanopathies, which are associated with loss of natively glycosylated ?-dystroglycan. Here we identify a new animal model for this class of disorders in Sphynx and Devon Rex cats. Affected cats displayed a slowly progressive myopathy with clinical and histologic hallmarks of muscular dystrophy including skeletal muscle weakness with

Paul T. Martin; G. Diane Shelton; Peter J. Dickinson; Beverly K. Sturges; Rui Xu; Richard A. LeCouteur; Ling T. Guo; Robert A. Grahn; Harriet P. Lo; Kathryn N. North; Richard Malik; Eva Engvall; Leslie A. Lyons

2008-01-01

260

Peripheral nerve involvement in merosin-deficient congenital muscular dystrophy and dy mouse  

Microsoft Academic Search

Merosin, also called laminin-2, is an isoform of laminin comprised of the ?2, ?1 and ?1 chains. Deficiency of merosin ?2 chain was recently identified as the primary cause of the classical form of congenital muscular dystrophy (CMD), an autosomal recessive neuromuscular disorder characterised by muscular dystrophy and brain white matter abnormalities. Interestingly, merosin-deficient CMD and its animal model dy

Kiichiro Matsumura; Hiroki Yamada; Fumiaki Saito; Yoshihide Sunada; Teruo Shimizu

1997-01-01

261

FrameShift Deletions in Patients with Duchenne and Becker Muscular Dystrophy  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD) and its less severe form Becker muscular dystrophy (BMD) are allelic disorders. It has been suggested that in the mutations involving BMD, the translational reading frame of messenger RNA is maintained and a smaller, though partially functional, protein is produced. In order to test this, the exon-intron boundaries of the first ten exons of the DMD

S. B. Malhotra; K. A. Hart; H. J. Klamut; N. S. T. Thomas; S. E. Bodrug; A. H. M. Burghes; M. Bobrow; P. S. Harper; M. W. Thompson; P. N. Ray; R. G. Worton

1988-01-01

262

Somatic mosaicism for a deletion of the dystrophin gene in a carrier of Becker muscular dystrophy  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD) and the allelic milder form of Becker muscular dystrophy (BMD) are caused by mutations of the dystrophin gene on the short arm of the X chromosome. One third of affected indviduals are expected to result from de novo mutations. Genetic counselling of families with sporadic cases is complicated by the potential meiotic origin of the mutation

T. Voit; E. Neuen-Jacob; V. Mahler; A. Jauch; M. Cremer

1992-01-01

263

Mutation analysis in Saudi Duchenne and Becker muscular dystrophy patients using multiplex PCR  

Microsoft Academic Search

IInnttrroodduuccttiioonn:: In Saudi Arabia, only limited work has been reported on the mutation patterns of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). This study looks at the spectrum of deletions in the 'hot spot' regions of the DMD gene in Saudi DMD\\/BMD patients using an enhanced multiplex PCR technique. M Maatteerriiaall aanndd mmeetthhooddss:: Twenty-six exons of the DMD

Adeel G. Chaudhary; Mohammed H. Alqahtani; Adel Abuzenadah; Mamdooh Gari; Abeer A. Al-Sofyani; Jumana Y. Al-Aama; Sahira A. Lary; Aisha H. Elaimi

2008-01-01

264

Molecular deletion patterns in Turkish Duchenne and Becker muscular dystrophy patients  

Microsoft Academic Search

The dystrophin gene deletion patterns of Duchenne \\/ Becker muscular dystrophy were investigated in 57 DMD, 7 BMD and 1 DMD-BMD intermediate muscular dystrophy patients. Deletions, analyzed by multiplex amplification of selected exons, were observed in 58% (38 cases) of the patients. It was found that exon 48 was the most frequently affected, while exon 44 was the least frequently

Pervin Dinçer; ?ükrüye Ayter; Meral Özgüç; Yavuz Renda

1996-01-01

265

Clinical Characteristics of Aged Becker Muscular Dystrophy Patients with Onset after 30 Years  

Microsoft Academic Search

To elucidate the clinical characteristics of aged patients with Becker muscular dystrophy (BMD), 4 patients with this disease who were over 50 years were examined. The ages at onset in all patients were later than 30 years. All were proven to have a deletion around exons 45–55 of the Duchenne muscular dystrophy (DMD) gene. Two patients became wheelchair bound in

Masahide Yazaki; Kunihiro Yoshida; Akinori Nakamura; Jun Koyama; Takashi Nanba; Nobuhira Ohori; Shu-ichi Ikeda

1999-01-01

266

Gene Therapy Strategies for Duchenne Muscular Dystrophy Utilizing Recombinant Adeno-associated Virus Vectors  

Microsoft Academic Search

Gene transfer vectors based on adeno-associated virus (AAV) are now widely used in the field of gene therapy. These vectors have been studied for their potential use in treating many diseases, among them the muscular dystrophies, the most common of which is Duchenne muscular dystrophy (DMD). Several recent advances in the areas of AAV serotype analysis, transgene engineering, and vector

Michael J. Blankinship; Paul Gregorevic; Jeffrey S. Chamberlain

2006-01-01

267

High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy  

Microsoft Academic Search

Daily prednisone improves strength in boys with Duchenne muscular dystrophy, but side effects are almost universal. We used a different dosing regimen of prednisone to determine if benefit to boys with Duchenne muscular dystrophy might be maintained with fewer side effects. Twice weekly oral prednisone was given each Friday and Saturday (5mg\\/kg\\/dose). This total dose is twice as high as

Anne M. Connolly; Jeanine Schierbecker; Renee Renna; Julaine Florence

2002-01-01

268

Meeting the Assistive Technology Needs of Students with Duchenne Muscular Dystrophy  

ERIC Educational Resources Information Center

|Students with Duchenne muscular dystrophy (DMD) have a degenerative disease that requires ongoing changes in assistive technology (AT). The AT team needs to be knowledgeable about the disease and its progression in order to meet these students' changing needs in a timely manner. The unique needs of students with Duchenne muscular dystrophy in…

Heller, Kathryn Wolff; Mezei, Peter J.; Avant, Mary Jane Thompson

2009-01-01

269

LARGE can functionally bypass ?-dystroglycan glycosylation defects in distinct congenital muscular dystrophies  

Microsoft Academic Search

Several congenital muscular dystrophies caused by defects in known or putative glycosyltransferases are commonly associated with hypoglycosylation of ?-dystroglycan (?-DG) and a marked reduction of its receptor function. We have investigated changes in the processing and function of ?-DG resulting from genetic manipulation of LARGE, the putative glycosyltransferase mutated both in Largemyd mice and in humans with congenital muscular dystrophy

Rita Barresi; Daniel E Michele; Motoi Kanagawa; Hollie A Harper; Sherri A Dovico; Jakob S Satz; Steven A Moore; Wenli Zhang; Harry Schachter; Jan P Dumanski; Ronald D Cohn; Ichizo Nishino; Kevin P Campbell

2004-01-01

270

Expression Profiling in the Muscular Dystrophies: Identification of Novel Aspects of Molecular Pathophysiology  

Microsoft Academic Search

We used expression profiling to define the pathophysiological cascades involved in the progres- sion of two muscular dystrophies with known primary biochemical defects, dystrophin deficiency (Duchenne muscular dystrophy) and a -sarcoglycan deficiency (a dystrophin-associated protein). We employed a novel protocol for expression profiling in human tissues using mixed samples of multiple patients and iterative com- parisons of duplicate datasets. We

Yi-Wen Chen; Po Zhao; Rehannah Borup; Eric P. Hoffman

2000-01-01

271

Thyroidal involvement in the expression of avian muscular dystrophy.  

PubMed

We showed previously that propylthiouracil (PTU), a thyroid inhibitor, could alleviate several major signs of hereditary muscular dystrophy in chickens. The goals of the present investigation were to: (1) determine whether a nearly athyroid condition (achieved within two days after hatching by surgical thyroidectomy plus PTU) during an 11-day period beneficially affects the dystrophic condition when followed by triiodothyronine (T3) replacement to 33 days of age; (2) determine the beneficial effects on the expression of avian dystrophy when the thyroidectomized-PTU-treated chickens received a wide range of moderate to low T3 replacement doses beginning by two days after thyroidectomy; and (3) examine the thyroid hormone receptor system in dystrophic muscle for a possible abnormality. Thyroid deprivation increased muscle function (righting ability) and reduced plasma creatine kinase activity in dystrophic chickens. The major thyroid-related abnormality in dystrophic pectoralis muscles was an increased maximum binding capacity of solubilized nuclear T3 receptors. PMID:1997792

King, D B; Entrikin, R K

1991-01-01

272

562. Ex Vivo Gene Therapy for Duchenne Muscular Dystrophy: Lentiviral Vectors, Exon Skipping and PhiC31 Integrase Approaches  

Microsoft Academic Search

Duchenne muscular dystrophy is the most severe muscular dystrophy. It is caused by the absence of dystrophin in muscle fibers. This absence lead to increased muscle damage, loss of muscle mass, loss of strength, respiratory and heart failure. This disease as currently no treatment. Myogenic cells transplantation is a possible cure for Duchenne muscular dystrophy. However, allogeneic graft success relies

Simon P. Quenneville; Pierre Chapdelaine; Joel Rousseau; Jacques P. Tremblay

2006-01-01

273

Health Care Utilization and Expenditures for Children and Young Adults With Muscular Dystrophy in a Privately Insured Population  

Microsoft Academic Search

We provide estimates of medical care utilization and expenditures for children and young adults younger than age 30 with muscular dystrophies in the United States. Accurate estimates are essential for calculations of lifetime costs and for economic evaluations of screening and management strategies for muscular dystrophy. We compare the medical expenditures for persons with muscular dystrophy with others by age

Lijing Ouyang; Scott D. Grosse; Aileen Kenneson

2008-01-01

274

Recent developments in the treatment of Duchenne muscular dystrophy and spinal muscular atrophy  

PubMed Central

Pediatric neuromuscular disorders comprise a large variety of disorders that can be classified based on their neuroanatomical localization, patterns of weakness, and laboratory test results. Over the last decade, the field of translational research has been active with many ongoing clinical trials. This is particularly so in two common pediatric neuromuscular disorders: Duchenne muscular dystrophy and spinal muscular atrophy. Although no definitive therapy has yet been found, numerous active areas of research raise the potential for novel therapies in these two disorders, offering hope for improved quality of life and life expectancy for affected individuals.

Liew, Wendy K. M.

2013-01-01

275

Multiple mutation in an extended Duchenne muscular dystrophy family.  

PubMed Central

We have investigated an extended pedigree with three cousins affected by Duchenne muscular dystrophy with apparent transmission through the male line. However, molecular studies have shown that one boy has a de novo duplication, another has a deletion, and the molecular mutation has yet to be defined in the third boy. All three X chromosomes in the affected boys appear to have a different origin. We speculate on the mechanisms by which the Duchenne locus may be particularly prone to mutation in this family and the possible involvement of transposons is discussed. Whatever the mechanism involved, the occurrence of three different mutations in one pedigree is a rare event. Images

Miciak, A; Keen, A; Jadayel, D; Bundey, S

1992-01-01

276

Mandibular distraction in a neonate with muscular dystrophy.  

PubMed

The following case report describes the successful use of distraction osteogenesis (DO) for the treatment of hypoplasia of the mandible in a patient with muscular dystrophy (MD). While DO has been used for hypoplasia of the mandible, no evidence exists that is it safe in the setting of MD. MD is a disease that primarily affects skeletal muscle; however, pathologic changes in the adjacent bone have been described. Furthermore, the healing of involved bone may be problematic, making DO a potentially unsuccessful technique in this group of patients. This report is the first successful utilization of DO for the treatment of mandibular hypoplasia in a patient with MD. PMID:16258306

Taub, Peter J; Koch, R Michael; Merer, David; Geldzahler, Gerald; Geldzhaler, Gerald

2005-11-01

277

The limb-girdle muscular dystrophies: diagnostic guidelines.  

PubMed

At least 11 different disorders can be recognized to be genetically distinct within the group of muscle diseases known as the limb-girdle muscular dystrophies. Direct gene or protein based tests are available to confirm the diagnosis in one autosomal dominant and six autosomal recessive forms. In these disorders, therefore, a definition based on molecular pathology is becoming possible. Clinical studies in the genetically defined subgroups may also help to determine phenotypic correlates for the various diseases. An integrated approach to diagnosis in this group, based on clinical observations supported by the result of genetic and protein studies, is likely to provide the optimum level of information. PMID:10700539

Bushby, K M

1999-01-01

278

Antisense mediated exon skipping therapy for duchenne muscular dystrophy (DMD)  

PubMed Central

Duchenne Muscular Dystrophy (DMD) is a lethal disease caused by mutations in the dystrophin gene (DMD) that result in the absence of essential muscle protein dystrophin. Among many different approaches for DMD treatment, exon skipping, mediated by antisense oligonucleotides, is one of the most promising methods for restoration of dystrophin expression. This approach has been tested extensively targeting different exons in numerous models both in vitro and in vivo. During the past 10 years, there has been a considerable progress by using DMD animal models involving three types of antisense oligonucleotides (2?-O-methyl phosphorothioate (2OME-PS), phosphorodiamidate morpholino oligomer (PMO)) and peptide nucleic acid (PNA).

Brolin, Camilla

2011-01-01

279

Usefulness of myocardial strain imaging in Duchenne muscular dystrophy.  

PubMed

Duchenne muscular dystrophy is an X-linked recessive disorder caused by the absence of dystrophin. Heart involvement is a classical complication in this disease and leads progressively to heart failure. Detecting latent myocardial involvement is essential in this disease because early use of drugs like angiotensin-converting enzyme inhibitors may delay the progression of heart disease. Myocardial strain imaging is an application of the tissue Doppler imaging. By assessing regional myocardial function, this tool might help clinicians to detect latent myocardial involvement in DMD patients. PMID:19036461

Fayssoil, A

2008-11-26

280

Autophagy as a new therapeutic target in Duchenne muscular dystrophy  

PubMed Central

A resolutive therapy for Duchene muscular dystrophy, a severe degenerative disease of the skeletal muscle, is still lacking. Because autophagy has been shown to be crucial in clearing dysfunctional organelles and in preventing tissue damage, we investigated its pathogenic role and its suitability as a target for new therapeutic interventions in Duchenne muscular dystrophy (DMD). Here we demonstrate that autophagy is severely impaired in muscles from patients affected by DMD and mdx mice, a model of the disease, with accumulation of damaged organelles. The defect in autophagy was accompanied by persistent activation via phosphorylation of Akt, mammalian target of rapamycin (mTOR) and of the autophagy-inhibiting pathways dependent on them, including the translation-initiation factor 4E-binding protein 1 and the ribosomal protein S6, and downregulation of the autophagy-inducing genes LC3, Atg12, Gabarapl1 and Bnip3. The defective autophagy was rescued in mdx mice by long-term exposure to a low-protein diet. The treatment led to normalisation of Akt and mTOR signalling; it also reduced significantly muscle inflammation, fibrosis and myofibre damage, leading to recovery of muscle function. This study highlights novel pathogenic aspects of DMD and suggests autophagy as a new effective therapeutic target. The treatment we propose can be safely applied and immediately tested for efficacy in humans.

De Palma, C; Morisi, F; Cheli, S; Pambianco, S; Cappello, V; Vezzoli, M; Rovere-Querini, P; Moggio, M; Ripolone, M; Francolini, M; Sandri, M; Clementi, E

2012-01-01

281

Drug screening in a zebrafish model of Duchenne muscular dystrophy  

PubMed Central

Two known zebrafish dystrophin mutants, sapje and sapje-like (sapc/100), represent excellent small-animal models of human muscular dystrophy. Using these dystrophin-null zebrafish, we have screened the Prestwick chemical library for small molecules that modulate the muscle phenotype in these fish. With a quick and easy birefringence assay, we have identified seven small molecules that influence muscle pathology in dystrophin-null zebrafish without restoration of dystrophin expression. Three of seven candidate chemicals restored normal birefringence and increased survival of dystrophin-null fish. One chemical, aminophylline, which is known to be a nonselective phosphodiesterase (PDE) inhibitor, had the greatest ability to restore normal muscle structure and up-regulate the cAMP-dependent PKA pathway in treated dystrophin-deficient fish. Moreover, other PDE inhibitors also reduced the percentage of affected sapje fish. The identification of compounds, especially PDE inhibitors, that moderate the muscle phenotype in these dystrophin-null zebrafish validates the screening protocol described here and may lead to candidate molecules to be used as therapeutic interventions in human muscular dystrophy.

Kawahara, Genri; Karpf, Jeremy A.; Myers, Jennifer A.; Alexander, Matthew S.; Guyon, Jeffrey R.; Kunkel, Louis M.

2011-01-01

282

Facioscapulohumeral muscular dystrophy in mice overexpressing FRG1.  

PubMed

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder that is not due to a classical mutation within a protein-coding gene. Instead, almost all FSHD patients carry deletions of an integral number of tandem 3.3-kilobase repeat units, termed D4Z4, located on chromosome 4q35 (ref. 3). D4Z4 contains a transcriptional silencer whose deletion leads to inappropriate overexpression in FSHD skeletal muscle of 4q35 genes located upstream of D4Z4 (ref. 4). To identify the gene responsible for FSHD pathogenesis, we generated transgenic mice selectively overexpressing in skeletal muscle the 4q35 genes FRG1, FRG2 or ANT1. We find that FRG1 transgenic mice develop a muscular dystrophy with features characteristic of the human disease; by contrast, FRG2 and ANT1 transgenic mice seem normal. FRG1 is a nuclear protein and several lines of evidence suggest it is involved in pre-messenger RNA splicing. We find that in muscle of FRG1 transgenic mice and FSHD patients, specific pre-mRNAs undergo aberrant alternative splicing. Collectively, our results suggest that FSHD results from inappropriate overexpression of FRG1 in skeletal muscle, which leads to abnormal alternative splicing of specific pre-mRNAs. PMID:16341202

Gabellini, Davide; D'Antona, Giuseppe; Moggio, Maurizio; Prelle, Alessandro; Zecca, Chiara; Adami, Raffaella; Angeletti, Barbara; Ciscato, Patrizia; Pellegrino, Maria Antonietta; Bottinelli, Roberto; Green, Michael R; Tupler, Rossella

2005-12-11

283

Restoring Dystrophin Expression in Duchenne Muscular Dystrophy Muscle  

PubMed Central

The identification of the Duchenne muscular dystrophy gene and protein in the late 1980s led to high hopes of rapid translation to molecular therapeutics. These hopes were fueled by early reports of delivering new functional genes to dystrophic muscle in mouse models using gene therapy and stem cell transplantation. However, significant barriers have thwarted translation of these approaches to true therapies, including insufficient therapeutic material (eg, cells and viral vectors), challenges in systemic delivery, and immunological hurdles. An alternative approach is to repair the patient's own gene. Two innovative small-molecule approaches have emerged as front-line molecular therapeutics: exon skipping and stop codon read through. Both approaches are in human clinical trials and aim to coax dystrophin protein production from otherwise inactive mutant genes. In the clinically severe dog model of Duchenne muscular dystrophy, the exon-skipping approach recently improved multiple functional outcomes. We discuss the status of these two methods aimed at inducing de novo dystrophin production from mutant genes and review implications for other disorders.

Hoffman, Eric P.; Bronson, Abby; Levin, Arthur A.; Takeda, Shin'ichi; Yokota, Toshifumi; Baudy, Andreas R.; Connor, Edward M.

2011-01-01

284

Dystrophin in frameshift deletion patients with Becker Muscular Dystrophy  

SciTech Connect

In a previous study the authors identified 14 cases with Duchenne muscular dystrophy (DMD) or its milder variant, Becker muscular dystrophy (BMD), with a deletion of exons 3-7, a deletion that would be expected to shift the translational reading frame of the mRNA and give a severe phenotype. They have examined dystrophin and its mRNA from muscle biopsies of seven cases with either mild or intermediate phenotypes. In all cases they detected slightly lower-molecular-weight dystrophin in 12%-15% abundance relative to the normal. By sequencing amplified mRNA they have found that exon 2 is spliced to exon 8, a splice that produces a frameshifted mRNA, and have found no evidence for alternate splicing that might be involved in restoration of dystrophin mRNA reading frame in the patients with a mild phenotype. Other transcriptional and posttranscriptional mechanisms such as cryptic promoter, ribosomal frameshifting, and reinitiation are suggested that might play some role in restoring the reading frame. 34 refs., 5 figs. 1 tab.

Gangopadhyay, S.B.; Ray, P.N.; Worton, R.G.; Sherratt, T.G.; Heckmatt, J.Z.; Dubowitz, V.; Strong, P.N.; Miller, G. (Penn State College of Medicine, Hershey, PA (United States)); Shokeir, M. (Univ. Hospital, Saskatchewan (Canada))

1992-09-01

285

Identification of Muscle-Specific MicroRNAs in Serum of Muscular Dystrophy Animal Models: Promising Novel Blood-Based Markers for Muscular Dystrophy  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder caused by mutations in the dystrophin gene, which encodes a cytoskeletal protein, dystrophin. Creatine kinase (CK) is generally used as a blood-based biomarker for muscular disease including DMD, but it is not always reliable since it is easily affected by stress to the body, such as exercise. Therefore, more reliable biomarkers

Hideya Mizuno; Akinori Nakamura; Yoshitsugu Aoki; Naoki Ito; Soichiro Kishi; Kazuhiro Yamamoto; Masayuki Sekiguchi; Shin'ichi Takeda; Kazuo Hashido; Sebastien Pfeffer

2011-01-01

286

Assessment of left ventricular systolic and diastolic functions in children with merosin-positive congenital muscular dystrophy  

Microsoft Academic Search

Cardiopathy is an expected finding in X-linked Duchenne and Becker muscular dystrophies. This holds true for some other forms such as autosomal recessive limb-girdle dystrophies. However, data on early-onset and usually severe congenital muscular dystrophies are limited. The purpose of this study was to investigate the presence of cardiac involvement in children with merosin-positive congenital muscular dystrophy. A total of

Naci Ceviz; Füsun Alehan; Dursun Alehan; ?encan Özme; Zuhal Akçören; Gülsev Kale; Haluk Topaloglu

2003-01-01

287

Proximal dystrophin gene deletions and protein alterations in becker muscular dystrophy.  

PubMed

Alterations in production of cytoskeletal protein dystrophin caused by in-frame gene mutations lead to the Becker muscular dystrophy. In this study we analyzed genotype-phenotype correlation in a group of Becker muscular dystrophy patients with deletions affecting the proximal part of dystrophin gene, encompassing exons 3-13. Four patients with deletions affecting N terminal dystrophin domain had early onset and faster progression of the disease, while three patients with deletions in the proximal part of dystrophin's rod domain had a more benign disease course. Our study suggests that proximal gene deletions in Becker muscular dystrophy have various phenotypic effects depending on the affected domain of protein dystrophin. PMID:16154963

Novakovi?, Ivana; Boji?, Dragana; Todorovi?, Slobodanka; Apostolski, Slobodan; Lukovi?, Ljiljana; Stefanovi?, Dejan; Milasin, Jelena

2005-06-01

288

Outpatient continuous inotrope infusion as an adjunct to heart failure therapy in Duchenne muscular dystrophy.  

PubMed

We report the use of continuous intravenous inotrope infusion as a palliative management strategy for the treatment of symptomatic, refractory, end stage cardiac dysfunction in patients with Duchenne muscular dystrophy. Milrinone and/or dobutamine administered by continuous intravenous infusion provided symptomatic and objective cardiovascular improvement up to 30 months in 3 individuals with Duchenne muscular dystrophy and severe dilated cardiomyopathy. Continuous inotrope infusion should be considered a practical treatment strategy for end stage cardiac dysfunction in Duchenne muscular dystrophy patients when cardiac transplantation is not a viable option. PMID:17005398

Cripe, Linda H; Barber, Brent J; Spicer, Robert L; Wong, Brenda L; Weidner, Norbert; Benson, D Woodrow; Markham, Larry W

2006-09-26

289

Parental Stress in Mothers of Boys with Duchenne Muscular Dystrophy  

PubMed Central

Objective To examine parental stress in mothers of boys with Duchenne muscular dystrophy (DMD). Method Stress and its predictors were examined in mothers of boys with DMD (n = 112). Comparisons were made with mothers of healthy children (n = 800), children with cerebral palsy (CP; n = 28), siblings of boys with DMD (n = 46), and longitudinally (n = 16). Results The presence of problem child behaviors consistently predicted maternal stress. Stress related to child behavior was higher in the DMD versus the normative group. No differences in stress were found in the DMD versus CP groups. Stress related to boys with DMD versus siblings was not significantly different. Over time, maternal stress related to child variables diminished. Conclusion Stress in mothers of boys with DMD is elevated, possibly due to increased problem behaviors, particularly in social interactions, rather than due to the physical demands of the disease alone.

Nereo, Nancy E.; Fee, Robert J.; Hinton, Veronica J.

2007-01-01

290

Human X chromosome markers and Duchenne muscular dystrophy.  

PubMed Central

Two DNA markers, a random DNA fragment 754 and the cDNA sequence encoding the gene for ornithine transcarbamylase (OTC) have been studied in kindreds segregating for Duchenne muscular dystrophy. 754 and OTC are located close physically to the mutation in the region Xp21 below the breakpoints in two Duchenne females. The genetic distance was found to be approximately 10cM between 754 and DMD (two crossovers in 26 meioses) and to be approximately 10cM between OTC and DMD (two crossovers in 26 meioses). Physical data suggest the order DMD-754-OTC. The frequency of recombination compared to physical distance between these markers and DMD suggests that there may be a hot spot of recombination. The relevance of these observations for the isolation of the DMD mutation and clinical use of these probes is discussed. Images

Davies, K E; Speer, A; Herrmann, F; Spiegler, A W; McGlade, S; Hofker, M H; Briand, P; Hanke, R; Schwartz, M; Steinbicker, V

1985-01-01

291

FSHD: copy number variations on the theme of muscular dystrophy  

PubMed Central

In humans, copy number variations (CNVs) are a common source of phenotypic diversity and disease susceptibility. Facioscapulohumeral muscular dystrophy (FSHD) is an important genetic disease caused by CNVs. It is an autosomal-dominant myopathy caused by a reduction in the copy number of the D4Z4 macrosatellite repeat located at chromosome 4q35. Interestingly, the reduction of D4Z4 copy number is not sufficient by itself to cause FSHD. A number of epigenetic events appear to affect the severity of the disease, its rate of progression, and the distribution of muscle weakness. Indeed, recent findings suggest that virtually all levels of epigenetic regulation, from DNA methylation to higher order chromosomal architecture, are altered at the disease locus, causing the de-regulation of 4q35 gene expression and ultimately FSHD.

Cabianca, Daphne Selvaggia

2010-01-01

292

Diphenoloxidases in X-linked recessive (Duchenne) muscular dystrophy.  

PubMed

In extracts derived from whole blood, a high molecular weight fraction of the diphenoloxidase enzymes has a significantly diminished specific activity in patients and definite carriers (heterozygotes) of the X-linked, recessive (Duchenne) form of muscular dystrophy. This anomaly was studied using spots of blood which had been collected on absorbent paper and stored at 4 degrees C for variable periods of time. Fractions enriched in the enzymes were obtained by subjecting aqueous extracts of the spots to treatment with an anion exchange resin (DEAE Sephadex A 50) followed by gel filtration on Sephadex G-25. It is of interest that this anomaly was observed in some definite carriers of the mutant gene who had on several occasions a serum creatine kinase level in the normal range. The significance of these observations is discussed. PMID:6799386

Demos, J J; Tuil, D G; Katz, P C; Berthelon, M A; Dautreaux, B; Premont, N

1981-01-01

293

Glycomic Analyses of Mouse Models of Congenital Muscular Dystrophy*  

PubMed Central

Dystroglycanopathies are a subset of congenital muscular dystrophies wherein ?-dystroglycan (?-DG) is hypoglycosylated. ?-DG is an extensively O-glycosylated extracellular matrix-binding protein and a key component of the dystrophin-glycoprotein complex. Previous studies have shown ?-DG to be post-translationally modified by both O-GalNAc- and O-mannose-initiated glycan structures. Mutations in defined or putative glycosyltransferase genes involved in O-mannosylation are associated with a loss of ligand-binding activity of ?-DG and are causal for various forms of congenital muscular dystrophy. In this study, we sought to perform glycomic analysis on brain O-linked glycan structures released from proteins of three different knock-out mouse models associated with O-mannosylation (POMGnT1, LARGE (Myd), and DAG1?/?). Using mass spectrometry approaches, we were able to identify nine O-mannose-initiated and 25 O-GalNAc-initiated glycan structures in wild-type littermate control mouse brains. Through our analysis, we were able to confirm that POMGnT1 is essential for the extension of all observed O-mannose glycan structures with ?1,2-linked GlcNAc. Loss of LARGE expression in the Myd mouse had no observable effect on the O-mannose-initiated glycan structures characterized here. Interestingly, we also determined that similar amounts of O-mannose-initiated glycan structures are present on brain proteins from ?-DG-lacking mice (DAG1) compared with wild-type mice, indicating that there must be additional proteins that are O-mannosylated in the mammalian brain. Our findings illustrate that classical ?1,2-elongation and ?1,6-GlcNAc branching of O-mannose glycan structures are dependent upon the POMGnT1 enzyme and that O-mannosylation is not limited solely to ?-DG in the brain.

Stalnaker, Stephanie H.; Aoki, Kazuhiro; Lim, Jae-Min; Porterfield, Mindy; Liu, Mian; Satz, Jakob S.; Buskirk, Sean; Xiong, Yufang; Zhang, Peng; Campbell, Kevin P.; Hu, Huaiyu; Live, David; Tiemeyer, Michael; Wells, Lance

2011-01-01

294

Glycomic analyses of mouse models of congenital muscular dystrophy.  

PubMed

Dystroglycanopathies are a subset of congenital muscular dystrophies wherein ?-dystroglycan (?-DG) is hypoglycosylated. ?-DG is an extensively O-glycosylated extracellular matrix-binding protein and a key component of the dystrophin-glycoprotein complex. Previous studies have shown ?-DG to be post-translationally modified by both O-GalNAc- and O-mannose-initiated glycan structures. Mutations in defined or putative glycosyltransferase genes involved in O-mannosylation are associated with a loss of ligand-binding activity of ?-DG and are causal for various forms of congenital muscular dystrophy. In this study, we sought to perform glycomic analysis on brain O-linked glycan structures released from proteins of three different knock-out mouse models associated with O-mannosylation (POMGnT1, LARGE (Myd), and DAG1(-/-)). Using mass spectrometry approaches, we were able to identify nine O-mannose-initiated and 25 O-GalNAc-initiated glycan structures in wild-type littermate control mouse brains. Through our analysis, we were able to confirm that POMGnT1 is essential for the extension of all observed O-mannose glycan structures with ?1,2-linked GlcNAc. Loss of LARGE expression in the Myd mouse had no observable effect on the O-mannose-initiated glycan structures characterized here. Interestingly, we also determined that similar amounts of O-mannose-initiated glycan structures are present on brain proteins from ?-DG-lacking mice (DAG1) compared with wild-type mice, indicating that there must be additional proteins that are O-mannosylated in the mammalian brain. Our findings illustrate that classical ?1,2-elongation and ?1,6-GlcNAc branching of O-mannose glycan structures are dependent upon the POMGnT1 enzyme and that O-mannosylation is not limited solely to ?-DG in the brain. PMID:21460210

Stalnaker, Stephanie H; Aoki, Kazuhiro; Lim, Jae-Min; Porterfield, Mindy; Liu, Mian; Satz, Jakob S; Buskirk, Sean; Xiong, Yufang; Zhang, Peng; Campbell, Kevin P; Hu, Huaiyu; Live, David; Tiemeyer, Michael; Wells, Lance

2011-04-01

295

Clinical features of facioscapulohumeral muscular dystrophy 2(CME)  

PubMed Central

Objective: In some 5% of patients with facioscapulohumeral muscular dystrophy (FSHD), no D4Z4 repeat contraction on chromosome 4q35 is observed. Such patients, termed patients with FSHD2, show loss of DNA methylation and heterochromatin markers at the D4Z4 repeat that are similar to patients with D4Z4 contractions (FSHD1). This commonality suggests that a change in D4Z4 chromatin structure unifies FSHD1 and FSHD2. The aim of our study was to critically evaluate the clinical features in patients with FSHD2 in order to establish whether these patients are phenotypically identical to FSHD1 and to establish the effects of the (epi-) genotype on the phenotype. Methods: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis. Results: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed. Conclusions: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process. GLOSSARY CSS = clinical severity score; FSHD = facioscapulohumeral muscular dystrophy; PBL = peripheral blood lymphocyte; SSLP = simple sequence length polymorphism.

de Greef, J.C.; Lemmers, R.J.L.F.; Camano, P.; Day, J.W.; Sacconi, S.; Dunand, M.; van Engelen, B.G.M.; Kiuru-Enari, S.; Padberg, G.W.; Rosa, A.L.; Desnuelle, C.; Spuler, S.; Tarnopolsky, M.; Venance, S.L.; Frants, R.R.; van der Maarel, S.M.; Tawil, R.

2010-01-01

296

Severe classical congenital muscular dystrophy and merosin expression.  

PubMed

It has been suggested that patients with autosomal recessive merosin deficient congenital muscular dystrophy (CMD), as opposed to the merosin positive cases form a homogeneous subgroup of a clinically more severe form of CMD. We examined merosin expression in muscle biopsies from five children with the severe classical form of CMD. Merosin deficiency was found only in 1 patient, a 6-year-old female, with abnormal brain myelination. However, her initial biopsy did not reveal the classical picture of dystrophy. The four merosin positive cases exhibited severe muscle weakness but their brain imagings were normal. There were no familial cases, except for the mother of 1 patient who had a milder form of the disease, suggesting an autosomal dominant mode of inheritance. In contrast to previous reports, the merosin deficient CMD cases were rare in our group. Furthermore, merosin positive cases were also associated with severe phenotype suggesting that a severe phenotype is not exclusive to merosin deficient cases. Finally, the absence of merosin in a neonate with hypotonia and weakness can be helpful in making a definitive diagnosis of CMD, even though the dystrophic process may not be evident yet and histology may be non-specific. PMID:9788720

Vajsar, J; Chitayat, D; Becker, L E; Ho, M; Ben-Zeev, B; Jay, V

1998-09-01

297

Diagnosis and cell-based therapy for Duchenne muscular dystrophy in humans, mice, and zebrafish  

PubMed Central

The muscular dystrophies are a heterogeneous group of genetically caused muscle degenerative disorders. The Kunkel laboratory has had a longstanding research program into the pathogenesis and treatment of these diseases. Starting with our identification of dystrophin as the defective protein in Duchenne muscular dystrophy (DMD), we have continued our work on normal dystrophin function and how it is altered in muscular dystrophy. Our work has led to the identification of the defective genes in three forms of limb girdle muscular dystrophy (LGMD) and a better understanding of how muscle degenerates in many of the different dystrophies. The identification of mutations causing human forms of dystrophy has lead to improved diagnosis for patients with the disease. We are continuing to improve the molecular diagnosis of the dystrophies and have developed a high-throughput sequencing approach for the low-cost rapid diagnosis of all known forms of dystrophy. In addition, we are continuing to work on therapies using available animal models. Currently, there are a number of mouse models of the human dystrophies, the most notable being the mdx mouse with dystrophin deficiency. These mice are being used to test possible therapies, including stem-cell-based approaches. We have been able to systemically deliver human dystrophin to these mice via the arterial circulation and convert 8% of dystrophin-deficient fibers to fibers expressing human dystrophin. We are now expanding our research to identify new forms of LGMD by analyzing zebrafish models of muscular dystrophy. Currently, we have 14 different zebrafish mutants exhibiting various phenotypes of muscular dystrophy, including muscle weakness and inactivity. One of these mutants carries a stop codon mutation in dystrophin, and we have recently identified another carrying a mutation in titin. We are currently positionally cloning the disease-causative mutation in the remaining 12 mutant strains. We hope that one of these new mutant strains of fish will have a mutation in a gene not previously implicated in human muscular dystrophy. This gene would become a candidate gene to be analyzed in patients which do not carry a mutation in any of the known dystrophy-associated genes. By studying both disease pathology and investigating potential therapies, we hope to make a positive difference in the lives of people living with muscular dystrophy.

Kunkel, Louis M.; Bachrach, Estanislao; Bennett, Richard R.; Guyon, Jeffrey; Steffen, Leta

2012-01-01

298

Congenital Muscular Dystrophy, White-Matter Abnormalities, and Neuronal Migration Disorders: The Expanding Concept  

Microsoft Academic Search

The congenital muscular dystrophies are a heterogeneous, recessively inherited group of disorders that have been subclassified on the basis of clinical central nervous system involvement. We report two children with \\

Mark T. Mackay; Andrew J. Kornberg; Lloyd Shield; Ethna Phelan; Michael J. Kean; Lee T. Coleman; Xenia Dennett

1998-01-01

299

Rimmed vacuoles in Becker muscular dystrophy have similar features with inclusion myopathies.  

PubMed

Rimmed vacuoles in myofibers are thought to be due to the accumulation of autophagic vacuoles, and can be characteristic in certain myopathies with protein inclusions in myofibers. In this study, we performed a detailed clinical, molecular, and pathological characterization of Becker muscular dystrophy patients who have rimmed vacuoles in muscles. Among 65 Becker muscular dystrophy patients, we identified 12 patients who have rimmed vacuoles and 11 patients who have deletions in exons 45-48 in DMD gene. All patients having rimmed vacuoles showed milder clinical features compared to those without rimmed vacuoles. Interestingly, the rimmed vacuoles in Becker muscular dystrophy muscles seem to represent autophagic vacuoles and are also associated with polyubiquitinated protein aggregates. These findings support the notion that rimmed vacuoles can appear in Becker muscular dystrophy, and may be related to the chronic changes in muscle pathology induced by certain mutations in the DMD gene. PMID:23251671

Momma, Kazunari; Noguchi, Satoru; Malicdan, May Christine V; Hayashi, Yukiko K; Minami, Narihiro; Kamakura, Keiko; Nonaka, Ikuya; Nishino, Ichizo

2012-12-14

300

Hypoplasia of the aorta in a patient diagnosed with LMNA gene mutation.  

PubMed

Hypoplasia of the aorta is a rare entity comprising tubular hypotrophy of a large segment of the thoracic and the abdominal aorta. We report for the first time the case of a 26-year-old man with Emery-Dreifuss muscular dystrophy presenting severe and diffuse hypoplasia of the aorta. PMID:22883396

Coutance, Guillaume; Labombarda, Fabien; Cauderlier, Emmanuelle; Belin, Annette; Richard, Pascale; Bonne, Gisèle; Chapon, Françoise

2012-08-07

301

Characterization of Adiposity and Metabolism in Lmna-Deficient Mice  

Microsoft Academic Search

Dunnigan's Familial Partial Lipodystrophy (FPLD) is an autosomal dominant disease characterized by regional fat loss and insulin resistance. FPLD is caused by mutations in the LMNA gene, which encodes intermediate filaments of the nuclear lamina. Different LMNA mutations cause Emery–Dreifuss muscular dystrophy and\\/or a dilated cardiomyopathy. It is not known how LMNA mutations cause any of the disease phenotypes. Here

Dedra A. Cutler; Teresa Sullivan; Bernice Marcus-Samuels; Colin L. Stewart; Marc L. Reitman

2002-01-01

302

Identification of muscle-specific microRNAs in serum of muscular dystrophy animal models: promising novel blood-based markers for muscular dystrophy.  

PubMed

Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder caused by mutations in the dystrophin gene, which encodes a cytoskeletal protein, dystrophin. Creatine kinase (CK) is generally used as a blood-based biomarker for muscular disease including DMD, but it is not always reliable since it is easily affected by stress to the body, such as exercise. Therefore, more reliable biomarkers of muscular dystrophy have long been desired. MicroRNAs (miRNAs) are small, ?22 nucleotide, noncoding RNAs which play important roles in the regulation of gene expression at the post-transcriptional level. Recently, it has been reported that miRNAs exist in blood. In this study, we hypothesized that the expression levels of specific serum circulating miRNAs may be useful to monitor the pathological progression of muscular diseases, and therefore explored the possibility of these miRNAs as new biomarkers for muscular diseases. To confirm this hypothesis, we quantified the expression levels of miRNAs in serum of the dystrophin-deficient muscular dystrophy mouse model, mdx, and the canine X-linked muscular dystrophy in Japan dog model (CXMD(J)), by real-time PCR. We found that the serum levels of several muscle-specific miRNAs (miR-1, miR-133a and miR-206) are increased in both mdx and CXMD(J). Interestingly, unlike CK levels, expression levels of these miRNAs in mdx serum are little influenced by exercise using treadmill. These results suggest that serum miRNAs are useful and reliable biomarkers for muscular dystrophy. PMID:21479190

Mizuno, Hideya; Nakamura, Akinori; Aoki, Yoshitsugu; Ito, Naoki; Kishi, Soichiro; Yamamoto, Kazuhiro; Sekiguchi, Masayuki; Takeda, Shin'ichi; Hashido, Kazuo

2011-03-30

303

Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials.  

PubMed

Duchenne muscular dystrophy is caused by mutations in the DMD gene that disrupt the open reading frame and prevent the full translation of its protein product, dystrophin. Restoration of the open reading frame and dystrophin production can be achieved by exon skipping using antisense oligonucleotides targeted to splicing elements. This approach aims to transform the Duchenne muscular dystrophy phenotype to that of the milder disorder, Becker muscular dystrophy, typically caused by in-frame dystrophin deletions that allow the production of an internally deleted but partially functional dystrophin. There is ongoing debate regarding the functional properties of the different internally deleted dystrophins produced by exon skipping for different mutations; more insight would be valuable to improve and better predict the outcome of exon skipping clinical trials. To this end, we have characterized the clinical phenotype of 17 patients with Becker muscular dystrophy harbouring in-frame deletions relevant to on-going or planned exon skipping clinical trials for Duchenne muscular dystrophy and correlated it to the levels of dystrophin, and dystrophin-associated protein expression. The cohort of 17 patients, selected exclusively on the basis of their genotype, included 4 asymptomatic, 12 mild and 1 severe patient. All patients had dystrophin levels of >40% of control and significantly higher dystrophin (P = 0.013), ?-dystroglycan (P = 0.025) and neuronal nitric oxide synthase (P = 0.034) expression was observed in asymptomatic individuals versus symptomatic patients with Becker muscular dystrophy. Furthermore, grouping the patients by deletion, patients with Becker muscular dystrophy with deletions with an end-point of exon 51 (the skipping of which could rescue the largest group of Duchenne muscular dystrophy deletions) showed significantly higher dystrophin levels (P = 0.034) than those with deletions ending with exon 53. This is the first quantitative study on both dystrophin and dystrophin-associated protein expression in patients with Becker muscular dystrophy with deletions relevant for on-going exon skipping trials in Duchenne muscular dystrophy. Taken together, our results indicate that all varieties of internally deleted dystrophin assessed in this study have the functional capability to provide a substantial clinical benefit to patients with Duchenne muscular dystrophy. PMID:22102647

Anthony, Karen; Cirak, Sebahattin; Torelli, Silvia; Tasca, Giorgio; Feng, Lucy; Arechavala-Gomeza, Virginia; Armaroli, Annarita; Guglieri, Michela; Straathof, Chiara S; Verschuuren, Jan J; Aartsma-Rus, Annemieke; Helderman-van den Enden, Paula; Bushby, Katherine; Straub, Volker; Sewry, Caroline; Ferlini, Alessandra; Ricci, Enzo; Morgan, Jennifer E; Muntoni, Francesco

2011-11-18

304

Strategy for mutation analysis in the autosomal recessive limb-girdle muscular dystrophies  

Microsoft Academic Search

We describe a strategy for molecular diagnosis in the autosomal recessive limb-girdle muscular dystrophies, a highly heterogeneous group of inherited muscle-wasting diseases. Genetic mutation analysis is directed by immunoanalysis of muscle biopsies using antibodies against a panel of muscular dystrophy-associated proteins. Performing the molecular analysis in this way greatly increases the chance that mutations will be found in the first

Robert Pogue; Louise V. B Anderson; Angela Pyle; Caroline Sewry; Christine Pollitt; Margaret A Johnson; Keith Davison; Jennifer A Moss; Eugenio Mercuri; Francesco Muntoni; Katherine M. D Bushby

2001-01-01

305

Dissociation of the dystroglycan complex in caveolin-3-deficient limb girdle muscular dystrophy  

Microsoft Academic Search

Limb girdle muscular dystrophy is a group of clinically and genetically heterogeneous disorders inherited in an autosomal recessive or dominant mode. Caveolin-3, the muscle-specific member of the caveolin gene family, is implicated in the patho- genesis of autosomal dominant limb girdle muscular dystrophy 1C. Here we report on a 4-year-old girl presenting with myalgia and muscle cramps due to a

Ralf Herrmann; Volker Straub; Martina Blank; Christian Kutzick; Nicola Franke; Eva Neuen Jacob; Hans-Gerd Lenard; Stephan Kröger; Thomas Voit

2000-01-01

306

Laminin ?2-chain gene mutations in two siblings presenting with limb-girdle muscular dystrophy  

Microsoft Academic Search

We report two siblings, an 11-year-old boy and his 7-year-old sister, referred to us with a diagnosis of muscular dystrophy. The boy presented at 22 months with delay in walking. A very high serum creatine kinase (CK) level and a dystrophic muscle biopsy lead to a diagnosis of Duchenne muscular dystrophy prior to the identification of the dystrophin gene. Two

I Naom; M D'Alessandro; C. A Sewry; J Philpot; A. Y Manzur; V Dubowitz; F Muntoni

1998-01-01

307

Protein and gene analyses of dysferlinopathy in a large group of Japanese muscular dystrophy patients  

Microsoft Academic Search

Mutations in the dysferlin gene cause muscular dystrophies called dysferlinopathy, which include limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM). To clarify the frequency, clinicopathological and genetic features of dysferlinopathy in Japan, we performed protein and gene analyses of dysferlin. We examined a total of 107 unrelated Japanese patients, including 53 unclassified LGMD, 28 MM and 26 other

Kazuhiko Tagawa; Megumu Ogawa; Kiyokazu Kawabe; Gaku Yamanaka; Tsuyoshi Matsumura; Kanako Goto; Ikuya Nonaka; Ichizo Nishino; Yukiko K. Hayashi

2003-01-01

308

Facioscapulohumeral Muscular Dystrophy Can Be a Cause of Isolated Childhood Cognitive Dysfunction  

Microsoft Academic Search

Facioscapulohumeral muscular dystrophy is one of the most prevalent muscular dystrophies in the world, resulting from the deletion of tandem repeats on chromosome 4q35. Extramuscular associations include sensorineural hearing loss, mental retardation, and epilepsy. These manifestations are commonly found in those with large deletions and early onset of weakness. A 26-year-old patient with a long-standing history of hearing loss, learning

Lisa D. Hobson-Webb

2006-01-01

309

mdxCv3 Mouse Is a Model for Electroretinography of Duchenne\\/Becker Muscular Dystrophy  

Microsoft Academic Search

Purpose. To identify an animal model for the abnormal scotopic electroretinogram found in a majority of Duchenne and Becker muscular dystrophy patients. Methods. Ganzfeld electroretinograms were recorded in dark-adapted normal C57BL\\/6 mice, and two strains of mice with different X-linked muscular dystrophy mutations {mdx and mdx Cv} ). Responses for the right eye were averaged and the amplitudes and implicit

De-Ann M. Pillers; Richard G. WeleberJtl; Verne M. Chapman; Peter N. Ray; William R. Woodward; Daniel G. Green

310

Developmental changes of radiological findings in Fukuyama-type congenital muscular dystrophy  

Microsoft Academic Search

Fukuyama-type congenital muscular dystrophy (FCMD) is characterized by congenital muscular dystrophy and associated with neuropathological\\u000a anomalies. However, the issue of whether the radiological findings of white-matter lesions represent delayed myelination,\\u000a demyelination or other problems remains controversial. We present serial radiological findings, including MR spectroscopy\\u000a (MRS), in a child with FCMD. These findings indicate a correlation between the imaging abnormalities and

Zenichiro Kato; Masahiro Morimoto; Kenji E. Orii; Tomomi Kato; Naomi Kondo

2010-01-01

311

Facioscapulohumeral muscular dystrophy presenting with unusual phenotypes and atypical morphological features of vacuolar myopathy  

Microsoft Academic Search

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy and usually follows an autosomal\\u000a dominant trait. Clinically, FSHD affects facial muscles and proximal upper limb and girdle muscles, but may present with variable\\u000a clinical phenotypes even within the same family. Most genetically confirmed FSHD patients exhibit unspecific morphological\\u000a signs of a degenerative myopathy. We report on five unrelated

Peter Reilich; Nicolai Schramm; Benedikt Schoser; Peter Schneiderat; Nicola Strigl-Pill; Josef Müller-Höcker; Wolfram Kress; Andreas Ferbert; Sabine Rudnik-Schöneborn; Johannes Noth; Hanns Lochmüller; Joachim Weis; Maggie C. Walter

2010-01-01

312

Different Molecular Signatures in Magnetic Resonance Imaging-Staged Facioscapulohumeral Muscular Dystrophy Muscles  

Microsoft Academic Search

BackgroundFacioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and is characterized by a non-conventional genetic mechanism activated by pathogenic D4Z4 repeat contractions. By muscle Magnetic Resonance Imaging (MRI) we observed that T2-short tau inversion recovery (T2-STIR) sequences identify two different conditions in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted

Giorgio Tasca; Mario Pescatori; Mauro Monforte; Massimiliano Mirabella; Elisabetta Iannaccone; Roberto Frusciante; Tiziana Cubeddu; Francesco Laschena; Pierfrancesco Ottaviani; Enzo Ricci

2012-01-01

313

Clinical and molecular analysis of a large family with three distinct phenotypes of progressive muscular dystrophy  

Microsoft Academic Search

Summary We describe a unique six-generation, highly consanguineous family originating from an isolated mountainous village in the Russian province of Daghestan. Three separate clinical phenotypes of progressive muscular dystrophy were identified in this large family. Seven patients developed a classical limb-girdle variant of muscular dystrophy (LGMD), with disease onset at 15-30 years and loss of ambulation within a 25-year course.

S. N. Illarioshkin; I. A. Ivanova-Smolenskaya; H. Tanaka; N. V. Vereshchagin; E. D. Markova; V. V. Poleshchuk; S. M. Lozhnikova; V. S. Sukhorukov; S. A. Limborska; P. A. Slominsky; K. B. Bulayeva; S. Tsuji

1996-01-01

314

Relatively low proportion of dystrophin gene deletions in Israeili Duchenne and Becker muscular dystrophy patients  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the X-linked dystrophin gene. The most common mutations in western populations are deletions that are spread non-randomly throughout the gene. Molecular analysis of the dystrophin gene structure by hybridization of the full length cDNA to Southern blots and by PCR in 62 unrelated Israeli

Ruth Shomrat; Eithan Gluck; Cyril Legum; Yosef Shiloh

1994-01-01

315

Exon-specific dystrophin antibodies for studies of duchenne muscular dystrophy  

Microsoft Academic Search

Exon-specific anti-dystrophin antibodies are used to monitor the success of treatments for Duchenne muscular dystrophy that\\u000a aim to restore the missing dystrophin protein. Dystrophin is a large cytoskeletal protein encoded by 79 exons and expressed\\u000a mainly in muscle. Most cases of Duchenne and Becker muscular dystrophies are caused by genetic deletion of one or more exons.\\u000a In-frame deletions permit some

Le Thanh Lam; Giang H. Nguyen; Nguyen thi Man; Caroline A. Sewry; Glenn E. Morris

2010-01-01

316

Adaptations to Exercise Training and Contraction-Induced Muscle Injury in Animal Models of Muscular Dystrophy  

Microsoft Academic Search

Carter GT, Abresch RT, Fowler WM Jr: Adaptations to exercise train- ing and contraction-induced muscle injury in animal models of muscular dystrophy. Am J Phys Med Rehabil 2002;81(Suppl):S151-S161. This article reviews the current status of exercise training and contrac- tion-induced muscle-injury investigations in animal models of muscular dystrophy. Most exercise-training studies have compared the adapta- tions of normal and dystrophic

Gregory T. Carter; R. Ted Abresch; William M. Fowler

2002-01-01

317

638. Therapeutic Antisense-Induced Exon Skipping for Duchenne Muscular Dystrophy  

Microsoft Academic Search

The severe Duchenne muscular dystrophy (DMD) is mostly caused by frame disrupting mutations in the dystrophin gene, which result in non-functional dystrophin proteins. Mutations that keep the reading frame intact give rise to internally deleted, semi-functional dystrophins and result in the milder Becker muscular dystrophy (BMD). Antisense oligonucleotides (AONs) have the potential to modulate the pre-mRNA splicing such that a

Annemieke Aartsma-Rus; Anneke A. M. Janson; Wendy E. Kaman; Mattie Bremmer-Bout; Christa L. de Winter; Habte F. Teshale; Gert-Jan B. van Ommen; Johan T. den Dunnen; Judith C. T. van Deutekom

2004-01-01

318

The Canadian experience with long-term deflazacort treatment in Duchenne muscular dystrophy.  

PubMed

Deflazacort is the most commonly prescribed corticosteroid for the treatment of Duchenne muscular dystrophy in Canada. We review the long-term experience with deflazacort treatment at two centers in Canada; Montreal and Toronto. Deflazacort has benefitted both cohorts by prolonged ambulation, preserved cardiac and respiratory function, less scoliosis and improved survival. Common side effects in both cohorts include weight gain, decreased height and cataract formation. The Canadian experience supports the use of deflazacort in treating boys with Duchenne muscular dystrophy. PMID:22655512

McAdam, Laura C; Mayo, Amanda L; Alman, Benjamin A; Biggar, W Douglas

2012-05-01

319

Abnormalities of the Electrocardiogram in Female Carriers of Duchenne Muscular Dystrophy  

Microsoft Academic Search

The algebraic sum of the R and S waves (R-S) in the V1 lead of the electrocardiogram has been found to be significantly greater in female carriers of X-linked Duchenne muscular dystrophy (but not in women with limb-girdle muscular dystrophy) compared with normal women of comparable age. A similar E.C.G. abnormality is found in affected boys, and possibly certain carriers

A. E. H. Emery

1969-01-01

320

Fukuyama-type congenital muscular dystrophy and defective glycosylation of ?-dystroglycan  

Microsoft Academic Search

Fukuyama-type congenital muscular dystrophy (FCMD) is a severe form of muscular dystrophy accompanied by abnormalities in\\u000a the eye and brain. The incidence of FCMD is particularly high in the Japanese population. Mutations in the fukutin gene have\\u000a been identified in patients with FCMD. Fukutin is predicted to be a Golgi apparatus resident protein and to be involved in\\u000a the post-translational

Fumiaki Saito; Kiichiro Matsumura

2011-01-01

321

Electrotransfer of naked DNA in the skeletal muscles of animal models of muscular dystrophies  

Microsoft Academic Search

The electrotransfer of naked DNA has recently been adapted to the transduction of skeletal muscle fibers. We investigated the short- and long-term efficacy of this methodology in wild-type animals and in mouse models of congenital muscular dystrophy (dy\\/dy, dy2J\\/dy2J), or Duchenne muscular dystrophy (mdx\\/mdx). Using a reporter construct, the short-term efficacy of fiber transduction reached 40% and was similar in

JT Vilquin; PF Kennel; M Paturneau-Jouas; P Chapdelaine; N Boissel; P Delaère; JP Tremblay; D Scherman; K Schwartz

2001-01-01

322

The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy  

Microsoft Academic Search

ALTHOUGH murine X-linked muscular dystrophy (mdx) and Duchenne muscular dystrophy (DMD) are genetically homologous and both characterized by a complete absence of dystrophin1,2, the limb muscles of adult mdx mice suffer neither the detectable weakness nor the progressive degeneration that are features of DMD3-8. Here we show that the mdx mouse diaphragm exhibits a pattern of degeneration, fibrosis and severe

H. H. Stedman; H. L. Sweeney; J. B. Shrager; H. C. Maguire; R. A. Panettieri; B. Petrof; M. Narusawa; J. M. Leferovich; J. T. Sladky; A. M. Kelly

1991-01-01

323

Facioscapulohumeral muscular dystrophy: a multicenter study on hearing function.  

PubMed

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant progressive myopathy, characteristically associated with a 4q35 deletion. In the unusual infantile-onset form of this degenerative disease, sensorineural hearing loss is a frequent clinical manifestation, whereas in patients with typical late-onset FSHD, investigations regarding hearing impairment yielded controversial results. We describe the findings of a multicenter investigation on possible auditory impairment in a series of 73 FSHD patients with a genetically confirmed diagnosis. Among them, 49 cases with no risk factors for deafness, aside from the disease, were identified by a clinical questionnaire and otoscopic examination (mean age 37.8 years, 31 males and 18 females). These subjects were evaluated by pure-tone audiometry. None were aware of hearing loss, while 4 had raised unilateral or bilateral pure-tone audiometric thresholds at 4000 and 8000 Hz, when evaluated by standardized tables. However, the mean raw pure-tone audiometric threshold values for these 49 cases were not significantly different from those of 55 controls (mean age 37.1 years, 32 males and 23 females). Moreover, by statistical analysis, age of onset, degree of muscular weakness and 4q35 EcoRI fragment size made no significant difference to auditory thresholds in our FSHD patients. Overall, the results of our multicenter study suggest that hearing loss in typical FSHD is not more prevalent than in the normal population. PMID:17715463

Trevisan, Carlo P; Pastorello, Ebe; Ermani, Mario; Angelini, Corrado; Tomelleri, Giuliano; Tonin, Paola; Mongini, Tiziana; Palmucci, Laura; Galluzzi, Giuliana; Tupler, Rossella G; Marioni, Gino; Rimini, Alessandro

2007-08-22

324

Merosin positive congenital muscular dystrophy with severe involvement of the central nervous system  

Microsoft Academic Search

Congenital muscular dystrophy (CMD) is one of the most frequent dystrophies of childhood, which is commonly characterized by neonatal muscle impairment with or without clinical evidence of central nervous system involvement. Several variants of CMD have been described and the disease has recently been classified into five clinically distinct forms: the two classical CMDs with and without deficit of the

Nicola De Stefano; Maria Teresa Dotti; Marcello Villanova; Gioacchino Scarano; Antonio Federico

1996-01-01

325

Developmental Defects in a Zebrafish Model for Muscular Dystrophies Associated with the Loss of Fukutin-Related Protein (FKRP)  

ERIC Educational Resources Information Center

|A number of muscular dystrophies are associated with the defective glycosylation of [alpha]-dystroglycan and many are now known to result from mutations in a number of genes encoding putative or known glycosyltransferases. These diseases include severe forms of congenital muscular dystrophy (CMD) such as Fukuyama type congenital muscular

Thornhill, Paul; Bassett, David; Lochmuller, Hanns; Bushby, Kate; Straub, Volker

2008-01-01

326

Effect of spinal surgery on lung function in Duchenne muscular dystrophy.  

PubMed Central

BACKGROUND--The effect on subsequent respiratory function of spinal stabilisation for scoliosis in Duchenne muscular dystrophy is unclear. In order to clarify this clinical problem, changes in the forced vital capacity of a group of children with Duchenne muscular dystrophy who had undergone spinal surgery were measured and compared with a group of children with Duchenne muscular dystrophy who had not had surgery. METHODS--In this retrospective study 17 boys with Duchenne muscular dystrophy who underwent spinal stabilisation at a mean age of 14.9 years (surgical group) were compared with 21 boys with Duchenne muscular dystrophy who had not had surgery (non-surgical group). The mean (SD) Cobb angle of the surgical group at 14.9 years was 57 (16.4) degrees, and of the non-surgical group at 15 years was 45 (29.9) degrees. Forced vital capacity expressed as percentage predicted (% FVC) was measured in total over a seven year period in the surgical group and over 6.5 years in the non-surgical group, and regression equations were calculated. Survival curves for both groups were also constructed. RESULTS--No difference was found between spinal stabilisation (surgical group) and the non-surgical group in the rate of deterioration of % FVC which was 3-5% per year. There was no difference in survival in either group. CONCLUSIONS--Spinal stabilisation in Duchenne muscular dystrophy does not alter the decline in pulmonary function, nor does it improve survival.

Kennedy, J D; Staples, A J; Brook, P D; Parsons, D W; Sutherland, A D; Martin, A J; Stern, L M; Foster, B K

1995-01-01

327

Merosin-positive congenital muscular dystrophy with mental retardation, microcephaly and central nervous system abnormalities unlinked to the Fukuyama muscular dystrophy and muscular–eye–brain loci: report of three siblings  

Microsoft Academic Search

Classical merosin (?2 laminin)-positive congenital muscular dystrophy is a heterogeneous subgroup of disorders; a few cases characterized by severe mental retardation, brain involvement and no ocular abnormalities were called Fukuyama-like congenital muscular dystrophy. We report a family of healthy non-consanguineous parents, with four affected siblings, of which one died at the age of 7 months due to an intercurrent illness,

V Ruggieri; F Lubieniecki; F Meli; D Diaz; E Ferragut; K Saito; M Brockington; F Muntoni; Y Fukuyama; A. L Taratuto

2001-01-01

328

Unexpected sarcolemmal complement membrane attack complex deposits on nonnecrotic muscle fibers in muscular dystrophies.  

PubMed

Antibody-dependent complement-mediated muscle fiber injury is a hypothetical immune effector response in inflammatory muscle diseases. Moreover, a sarcolemmal alteration in muscular dystrophies might trigger antibody-independent activation of the alternative complement pathway. We therefore searched for C5b9 complement membrane attack complex (MAC), immunoglobulin (Ig)G, and IgM deposits on nonnecrotic muscle fibers in muscle specimens from 81 patients with inflammatory myopathies, 45 patients with muscular dystrophies, and 19 patients with necrotizing myopathies. Sarcolemmal MAC deposits were present on nonnecrotic fibers (C+ fibers) in only two unusual types of inflammatory myopathy. By contrast, seven of 17 facioscapulohumeral dystrophy, four of nine limb-girdle dystrophy, and three of six merosin (laminin-alpha-2)-positive congenital muscular dystrophy but none of the Becker or Duchenne dystrophy specimens harbored C+ fibers. None of the C+ fibers immunostained for IgG or IgM, and none failed to immunostain for CD59 or CD46-inhibitors of the complement cascade. Our findings do not support a role for antibody-dependent complement-mediated muscle fiber injury in the major inflammatory muscle diseases. The cause and pathogenetic significance of the C+ fibers in the different types of muscular dystrophies remains to be elucidated. PMID:9443455

Spuler, S; Engel, A G

1998-01-01

329

From representation to mediation: The shaping of collective mobilization on muscular dystrophy in France  

Microsoft Academic Search

How, and to what extent, do patient organisations renew traditional forms of social participation and protest? This question is examined, drawing on a socio-historical case study of the Association Française contre les Myopathies—French Muscular Dystrophy Organisation (AFM). The originality of the AFM is that it has not been content to endorse the classic role of representation of people with muscular

Vololona Rabeharisoa

2006-01-01

330

A Trial of Selenium and Vitamin E in Boys With Muscular Dystrophy  

Microsoft Academic Search

The administration of selenium and vitamin E was tried in a group of 20 boys with muscular dystrophy. Muscular strength was measured at intervals of 6 months. The boys were treated for 1 year (selenium 6 ?g\\/kg for 6 months and 20 ?g\\/kg for 6 months), followed by 1 year of no treatment. The whole series was completed in 16

I. Gamstorp; K. H. Gustavson; O. Hellström; B. Nordgren

1986-01-01

331

Some Dynamics of Personality Development in Boys Suffering from Muscular Dystrophy  

ERIC Educational Resources Information Center

|Discussed are personality aspects of Duchenne or pseudohypertrophic muscular dystrophy, a progressive wasting of muscular tissue, which afflicts only boys, and usually has its noticeable onset before the age of 6 years; and described is the development of three male dystrophic siblings. (DB)|

Mearig, Judith S.

1973-01-01

332

Investigation of Poor Academic Achievement in Children with Duchenne Muscular Dystrophy  

ERIC Educational Resources Information Center

|Duchenne Muscular Dystrophy (DMD) is a neurogenetic developmental disorder that presents with progressive muscular weakness. It is caused by a mutation in a gene that results in the absence of specific products that normally localize to muscle cells and the central nervous system (CNS). The majority of affected individuals have IQs within the…

Hinton, V. J.; De Vivo, D. C.; Fee, R.; Goldstein, E.; Stern, Y.

2004-01-01

333

Vascular-targeted therapies for Duchenne muscular dystrophy  

PubMed Central

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy and an X-linked recessive, progressive muscle wasting disease caused by the absence of a functional dystrophin protein. Dystrophin has a structural role as a cytoskeletal stabilization protein and protects cells against contraction-induced damage. Dystrophin also serves a signaling role through mechanotransduction of forces and localization of neuronal nitric oxide synthase (nNOS), which produces nitric oxide (NO) to facilitate vasorelaxation. In DMD, the signaling defects produce inadequate tissue perfusion caused by functional ischemia due to a diminished ability to respond to shear stress induced endothelium-dependent dilation. Additionally, the structural defects seen in DMD render myocytes with an increased susceptibility to mechanical stress. The combination of both defects is necessary to generate myocyte damage, which induces successive rounds of myofiber degeneration and regeneration, loss of calcium homeostasis, chronic inflammatory response, fibrosis, and myonecrosis. In individuals with DMD, these processes inevitably cause loss of ambulation shortly after the first decade and an abbreviated life with death in the third or fourth decade due to cardio-respiratory anomalies. There is no known cure for DMD, and although the culpable gene has been identified for more than twenty years, research on treatments has produced few clinically relevant results. Several recent studies on novel DMD therapeutics are vascular targeted and focused on attenuating the inherent functional ischemia. One approach improves vasorelaxation capacity through pharmaceutical inhibition of either phosphodiesterase 5 (PDE5) or angiotensin-converting enzyme (ACE). Another approach increases the density of the underlying vascular network by inducing angiogenesis, and this has been accomplished through either direct delivery of vascular endothelial growth factor (VEGF) or by downregulating the VEGF decoy-receptor type 1 (VEGFR-1 or Flt-1). The pro-angiogenic approaches also seem to be pro-myogenic and could resolve the age-related decline in satellite cell (SC) quantity seen in mdx models through expansion of the SC juxtavascular niche. Here we review these four vascular targeted treatment strategies for DMD and discuss mechanisms, proof of concept, and the potential for clinical relevance associated with each therapy.

2013-01-01

334

Vascular-targeted therapies for Duchenne muscular dystrophy.  

PubMed

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy and an X-linked recessive, progressive muscle wasting disease caused by the absence of a functional dystrophin protein. Dystrophin has a structural role as a cytoskeletal stabilization protein and protects cells against contraction-induced damage. Dystrophin also serves a signaling role through mechanotransduction of forces and localization of neuronal nitric oxide synthase (nNOS), which produces nitric oxide (NO) to facilitate vasorelaxation. In DMD, the signaling defects produce inadequate tissue perfusion caused by functional ischemia due to a diminished ability to respond to shear stress induced endothelium-dependent dilation. Additionally, the structural defects seen in DMD render myocytes with an increased susceptibility to mechanical stress. The combination of both defects is necessary to generate myocyte damage, which induces successive rounds of myofiber degeneration and regeneration, loss of calcium homeostasis, chronic inflammatory response, fibrosis, and myonecrosis. In individuals with DMD, these processes inevitably cause loss of ambulation shortly after the first decade and an abbreviated life with death in the third or fourth decade due to cardio-respiratory anomalies. There is no known cure for DMD, and although the culpable gene has been identified for more than twenty years, research on treatments has produced few clinically relevant results. Several recent studies on novel DMD therapeutics are vascular targeted and focused on attenuating the inherent functional ischemia. One approach improves vasorelaxation capacity through pharmaceutical inhibition of either phosphodiesterase 5 (PDE5) or angiotensin-converting enzyme (ACE). Another approach increases the density of the underlying vascular network by inducing angiogenesis, and this has been accomplished through either direct delivery of vascular endothelial growth factor (VEGF) or by downregulating the VEGF decoy-receptor type 1 (VEGFR-1 or Flt-1). The pro-angiogenic approaches also seem to be pro-myogenic and could resolve the age-related decline in satellite cell (SC) quantity seen in mdx models through expansion of the SC juxtavascular niche. Here we review these four vascular targeted treatment strategies for DMD and discuss mechanisms, proof of concept, and the potential for clinical relevance associated with each therapy. PMID:23618411

Ennen, James P; Verma, Mayank; Asakura, Atsushi

2013-04-23

335

Progressive muscular dystrophy with congenital adrenal hypoplasia: an unusual autopsy case.  

PubMed

A 3 1/2-year-old child with progressive muscular dystrophy (PMD) and congenital adrenal hypoplasia (CAH) is described. Symptoms and signs of adrenocortical insufficiency appeared shortly after birth. Despite corticosteroid therapy, the muscular weakness and elevated CK level continued. A diagnosis of Duchenne muscular dystrophy was made on the basis of clinical signs and characteristic muscle biopsy. The affection of his older brother suggests an X-linked recessive inheritance. The autopsy revealed a very rare combination of cytomegalic type CAH and PMD. This combination suggests that a small deletion of X-chromosome might be responsible for the two disorders. PMID:3766905

Toyofuku, T; Takashima, S; Takeshita, K; Nagafuji, H

1986-01-01

336

Scoliosis correction with pedicle screws in Duchenne muscular dystrophy  

PubMed Central

This report describes the spinal fixation with pedicle-screw-alone constructs for the posterior correction of scoliosis in patients suffering from Duchene muscular dystrophy (DMD). Twenty consecutive patients were prospectively followed up for an average of 5.2 years (min 2 years). All patients were instrumented from T3/T4 to the pelvis. Pelvic fixation was done with iliac screws similar to Galveston technique. The combination of L5 pedicle screws and iliac screws provided a stable caudal foundation. An average of 16 pedicle screws was used per patient. The mean total blood loss was 3.7 l, stay at the intensive care unit was 77 h and hospital stay was 19 days. Rigid stabilisation allowed immediate mobilisation of the patient in the wheel chair. Cobb angle improved 77% from 44° to 10°, pelvic tilt improved 65% from 14° to 3°. Lumbar lordosis improved significantly from 20° to 49°, thoracic kyphosis remained unchanged. No problems related to iliac fixation, no pseudarthrosis or implant failures were observed. The average percentage of predicted forced vital capacity (%FVC) of the patients was 55% (22–94%) preoperatively and decreased to 44% at the last follow-up. There were no pulmonary complications. One patient with a known cardiomyopathy died intraoperatively due to a sudden cardiac arrest. The rigid primary stability with pedicle screws allowed early mobilisation of the patients, which helped to avoid pulmonary complications.

Hahn, Frederik; Hauser, Dominik; Espinosa, Norman; Blumenthal, Stefan

2007-01-01

337

Muscular dystrophy in dysferlin-deficient mouse models.  

PubMed

Mutations in the dysferlin gene result in the development of a range of early adult-onset, progressive muscular dystrophies, collectively known as the dysferlinopathies. There is currently no effective treatment for these disorders. Several spontaneous and engineered alleles at the mouse dysferlin locus have been isolated and these dysferlin-deficient mouse strains are providing valuable insights into the role dysferlin plays in skeletal muscle physiology, heart function, and the regulation of the innate immune system. In addition, mouse models of dysferlinopathy are now widely used to test novel therapeutic strategies. Each dysferlin-deficient mouse strain has been characterised to varying degrees using a variety of histological and functional assays, occasionally producing results inconsistent with other strains. Here, we review each mouse model and physiological changes in various systems which accompany their muscle disease with emphasis on the how the disease process develops in different mouse models of dysferlinopathy. This review highlights the urgent requirement for standardised assays and outcome measures that will unify and coordinate research efforts throughout the field, procedures that are necessary if potential therapies are to be tested efficiently and effectively. PMID:23473732

Hornsey, Mark A; Laval, Steven H; Barresi, Rita; Lochmüller, Hanns; Bushby, Kate

2013-03-07

338

Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers  

PubMed Central

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by contractions of repetitive elements within the macrosatellite D4Z4 on chromosome 4q35. The pathophysiology of FSHD is unknown and, as a result, there is currently no effective treatment available for this disease. To better understand the pathophysiology of FSHD and develop mRNA-based biomarkers of affected muscles, we compared global analysis of gene expression in two distinct muscles obtained from a large number of FSHD subjects and their unaffected first-degree relatives. Gene expression in two muscle types was analyzed using GeneChip Gene 1.0 ST arrays: biceps, which typically shows an early and severe disease involvement; and deltoid, which is relatively uninvolved. For both muscle types, the expression differences were mild: using relaxed cutoffs for differential expression (fold change ?1.2; nominal P value <0.01), we identified 191 and 110 genes differentially expressed between affected and control samples of biceps and deltoid muscle tissues, respectively, with 29 genes in common. Controlling for a false-discovery rate of <0.25 reduced the number of differentially expressed genes in biceps to 188 and in deltoid to 7. Expression levels of 15 genes altered in this study were used as a “molecular signature” in a validation study of an additional 26 subjects and predicted them as FSHD or control with 90% accuracy based on biceps and 80% accuracy based on deltoids.

Rahimov, Fedik; King, Oliver D.; Leung, Doris G.; Bibat, Genila M.; Emerson, Charles P.; Kunkel, Louis M.; Wagner, Kathryn R.

2012-01-01

339

Genetic heterogeneity in 30 German patients with oculopharyngeal muscular dystrophy.  

PubMed

Oculopharyngeal muscular dystrophy (OPMD) is due to short elongations of a polyalanine tract in the poly(A) binding protein nuclear 1 (PABPN1) gene. Originally GCG expansions in which (GCG)(6) is extended to (GCG)(7-13) were found. Subsequently five further genotypes with additional GCA- and GCG-trinucleotides were identified in single OPMD patients. This indicated larger genetic heterogeneity and showed that unequal crossing-over and not replication slippage must be the underlying mechanism of elongation.We performed sequencing of the PABPN1 gene in 30 German OPDM index patients to determine the exact genotype. The original GCG expansion ranging from (GCG)(8) to (GCG)(11) was found in 22 patients. In 8 patients, however, three different elongated alleles other than classical (GCG)(7-13) were observed. Two of these genotypes had already been identified in Japanese patients. One genotype was recently identified showing (GCG)(6) followed by inserted (GCA)(3)GCG in four unrelated patients. This study further supports the theory of unequal crossing over as the molecular mechanism leading to elongation. It shows that other genotypes than classical (GCG)(7-13) are rather common in German OPMD patients. The data imply that there is no single founder effect in German OPMD patients. PMID:16619122

Müller, T; Deschauer, M; Kolbe-Fehr, F; Zierz, St

2006-04-20

340

Oculopharyngeal muscular dystrophy - an under-diagnosed disorder?  

PubMed

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant muscle disorder, usually of late onset. OPMD is among the few triplet repeat diseases/ polyalanine (poly(A)) expansion diseases for which the function of the mutated gene is quite well established. The disease is characterised by slowly progressive bilateral ptosis, dysphagia and proximal limb weakness, appearing after the age of 40 years. Prevalence and incidence of OPMD are low, but the disease occurs all over the world. The pedigrees of two Swiss kindred have been previously reported in Switzerland. In the last 2 years, accumulation of newly diagnosed cases in North-West Switzerland have been observed, which suggests that OPMD may be more prevalent than previously thought. Primary care providers, opthalmologists and neurologists that are alert for the almost specific combination of clinical signs, together with the availability of reliable genetic testing may help to recognise currently undiagnosed patients. They can advance knowledge and the characterisation of the OPMD population in Switzerland. Since the number of disorders linked to poly(A) expansions is growing rapidly, the study of OPMD may contribute to the understanding of a large group of other developmental and degenerative diseases. On the basis of a patient with "classical" OPMD, this review summarises the clinical, therapeutic, epidemiological, pathomechanistic and genetic aspects of OPMD, provides practical information about the differential diagnosis of OPMD, and presents a survey of different investigational methods. PMID:16333769

Rüegg, Stephan; Lehky Hagen, Monique; Hohl, Ursula; Kappos, Ludwig; Fuhr, Peter; Plasilov, Martina; Müller, Hansjakob; Heinimann, Karl

2005-10-01

341

Catheter Ablation of Multiple Accessory Pathways in Duchenne Muscular Dystrophy  

PubMed Central

A 23-year-old male with Duchenne muscular dystrophy (DMD) experienced self-limiting palpitations at age 19 years for the first time. Palpitations recurred not earlier than at age 23 years, and were attributed to narrow complex tachycardia, which could be terminated with adenosine. Since electrocardiography showed a delta-wave, Wolff-Parkinson-White (WPW) syndrome was diagnosed, ajmaline prescribed and radio-frequency catheter ablation of three accessory pathways carried out one week later. One day after ablation, however, a relapse of the supraventricular tachycardia occurred and was terminated with ajmaline. Re-entry tachycardia occurred a second time six days after ablation, and as before, it was stopped only with ajmaline. Despite administration of verapamil to prevent tachycardia, it occurred a third time four months after ablation. This case shows that cardiac involvement in DMD may manifest also as WPW-syndrome. In these patients, repeated radio-frequency catheter ablation of accessory pathways may be necessary to completely block the re-entry mechanism.

Stollberger, Claudia; Steger, Christine; Gatterer, Edmund

2013-01-01

342

Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy.  

PubMed Central

Neuronal nitric oxide synthase (nNOS) in fast-twitch skeletal muscle fibers is primarily particulate in contrast to its greater solubility in brain. Immunohistochemistry shows nNOS localized to the sarcolemma, with enrichment at force transmitting sites, the myotendinous junctions, and costameres. Because this distribution is similar to dystrophin, we determined if nNOS expression was affected by the loss of dystrophin. Significant nNOS immunoreactivity and enzyme activity was absent in skeletal muscle tissues from patients with Duchenne muscular dystrophy. Similarly, in dystrophin-deficient skeletal muscles from mdx mice both soluble and particulate nNOS was greatly reduced compared with C57 control mice. nNOS mRNA was also reduced in mdx muscle in contrast to mRNA levels for a dystrophin binding protein, alpha 1-syntrophin. nNOS levels increased dramatically from 2 to 52 weeks of age in C57 skeletal muscle, which may indicate a physiological role for NO in aging-related processes. Biochemical purification readily dissociates nNOS from the dystrophin-glycoprotein complex. Thus, nNOS is not an integral component of the dystrophin-glycoprotein complex and is not simply another dystrophin-associated protein since the expression of both nNOS mRNA and protein is affected by dystrophin expression. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4

Chang, W J; Iannaccone, S T; Lau, K S; Masters, B S; McCabe, T J; McMillan, K; Padre, R C; Spencer, M J; Tidball, J G; Stull, J T

1996-01-01

343

Catheter ablation of multiple accessory pathways in duchenne muscular dystrophy.  

PubMed

A 23-year-old male with Duchenne muscular dystrophy (DMD) experienced self-limiting palpitations at age 19 years for the first time. Palpitations recurred not earlier than at age 23 years, and were attributed to narrow complex tachycardia, which could be terminated with adenosine. Since electrocardiography showed a delta-wave, Wolff-Parkinson-White (WPW) syndrome was diagnosed, ajmaline prescribed and radio-frequency catheter ablation of three accessory pathways carried out one week later. One day after ablation, however, a relapse of the supraventricular tachycardia occurred and was terminated with ajmaline. Re-entry tachycardia occurred a second time six days after ablation, and as before, it was stopped only with ajmaline. Despite administration of verapamil to prevent tachycardia, it occurred a third time four months after ablation. This case shows that cardiac involvement in DMD may manifest also as WPW-syndrome. In these patients, repeated radio-frequency catheter ablation of accessory pathways may be necessary to completely block the re-entry mechanism. PMID:23508228

Finsterer, Josef; Stöllberger, Claudia; Steger, Christine; Gatterer, Edmund

2013-02-28

344

Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy  

PubMed Central

Muscular dystrophies comprise a diverse group of genetic disorders that lead to muscle wasting and, in many instances, premature death1. Many mutations that cause muscular dystrophy compromise the support network that connects myofilament proteins within the cell to the basal lamina outside the cell, rendering the sarcolemma more permeable or leaky. Here we show that deletion of the gene encoding cyclophilin D (Ppif) rendered mitochondria largely insensitive to the calcium overload–induced swelling associated with a defective sarcolemma, thus reducing myofiber necrosis in two distinct models of muscular dystrophy. Mice lacking ?-sarcoglycan (Scgd?/? mice) showed markedly less dystrophic disease in both skeletal muscle and heart in the absence of Ppif. Moreover, the premature lethality associated with deletion of Lama2, encoding the ?-2 chain of laminin-2, was rescued, as were other indices of dystrophic disease. Treatment with the cyclophilin inhibitor Debio-025 similarly reduced mitochondrial swelling and necrotic disease manifestations in mdx mice, a model of Duchenne muscular dystrophy, and in Scgd?/? mice. Thus, mitochondrial-dependent necrosis represents a prominent disease mechanism in muscular dystrophy, suggesting that inhibition of cyclophilin D could provide a new pharmacologic treatment strategy for these diseases.

Millay, Douglas P; Sargent, Michelle A; Osinska, Hanna; Baines, Christopher P; Barton, Elisabeth R; Vuagniaux, Gregoire; Sweeney, H Lee; Robbins, Jeffrey; Molkentin, Jeffery D

2009-01-01

345

Merosin-positive congenital muscular dystrophy with mental retardation, microcephaly and central nervous system abnormalities unlinked to the Fukuyama muscular dystrophy and muscular-eye-brain loci: report of three siblings.  

PubMed

Classical merosin (2 laminin)-positive congenital muscular dystrophy is a heterogeneous subgroup of disorders; a few cases characterized by severe mental retardation, brain involvement and no ocular abnormalities were called Fukuyama-like congenital muscular dystrophy. We report a family of healthy non-consanguineous parents, with four affected siblings, of which one died at the age of 7 months due to an intercurrent illness, who presented congenital hypotonia, severe mental retardation, microcephaly, delayed psychomotor development, generalized muscular wasting and weakness with mild facial involvement, calf pseudohypertrophy, joint contractures and areflexia. Muscle biopsy disclosed severe muscular dystrophy. Immunostaining for laminin 2 80 kDa and clone Mer3/22B2 monoclonal antibodies, 1 and 1 chain was preserved. Magnetic resonance imaging findings were consistent with pontocerebellar hypoplasia, bilateral opercular abnormalities and focal cortical dysplasia as well as minute periventricular white matter changes. Clusters of small T2-weighted focal hyperintensities in both cerebellar hemispheres consistent with cysts were observed in two of the three siblings studied with magnetic resonance imaging. Ophthalmologic and cardiologic examination was normal. Haplotype analysis using microsatellite markers excluded the Fukuyama congenital muscular dystrophy, LAMA2 and muscle-eye-brain disease loci. Thus, a wider spectrum of phenotypes, gene defects and protein deficiencies might be involved in congenital muscular dystrophy with brain abnormalities. PMID:11525887

Ruggieri, V; Lubieniecki, F; Meli, F; Diaz, D; Ferragut, E; Saito, K; Brockington, M; Muntoni, F; Fukuyama, Y; Taratuto, A L

2001-09-01

346

[The development of an ultrasound-mediated nucleic acid delivery system for treating muscular dystrophies].  

PubMed

Muscular dystrophies are a group of heterogeneous diseases that are characterized by progressive muscle weakness, wasting and degeneration. These muscular deficiencies are often caused by the loss of the protein dystrophin, a crucial element of the dystrophin-glycoprotein complex of muscle fibers. Duchenne muscular dystrophy (DMD) is a fatal, X-linked muscular disease that occurs in 1 out of every 3500 males. Therefore, feasible strategies for replacing or repairing the defective gene are required; however, to date, no effective therapeutic strategies for muscular dystrophies have been established. In this review, we first introduce gene therapies mediated by adeno-associated viruses (AAVs) including a functional dystrophin cDNA or antisense oligonucleotide (AO)-induced exon-skipping therapies, which are designed to exclude the mutated or additional exon(s) in the defective gene and thereby correct the translational reading frame. Recently, we developed "Bubble liposomes" (BLs), which are polyethylene glycol (PEG)-modified liposomes entrapping echo-contrast gas that is known as ultrasound (US) imaging gas. BL application combined with US exposure can function as a novel gene delivery tool, and we demonstrate that the US-mediated eruption of BLs is a feasible and efficient technique to deliver plasmid DNA or AOs for the treatment of muscular dystrophies. PMID:23208045

Negishi, Yoichi; Hamano, Nobuhito; Shiono, Hitomi; Akiyama, Saki; Endo-Takahashi, Yoko; Suzuki, Ryo; Maruyama, Kazuo; Aramaki, Yukihiko

2012-01-01

347

Muscle MRI findings in patients with limb girdle muscular dystrophy with calpain 3 deficiency (LGMD2A) and early contractures  

Microsoft Academic Search

Limb girdle muscular dystrophy 2A is a common variant secondary to mutations in the calpain 3 gene. A proportion of patients has early and severe contractures, which can cause diagnostic difficulties with other conditions. We report clinical and muscle magnetic resonance imaging findings in seven limb girdle muscular dystrophy 2A patients (four sporadic and three familial) who had prominent and

Eugenio Mercuri; Kate Bushby; Enzo Ricci; Daniel Birchall; Marika Pane; Maria Kinali; Joanna Allsop; Vincenzo Nigro; Amets Sáenz; Annachiara Nascimbeni; Luigi Fulizio; Corrado Angelini; Francesco Muntoni

2005-01-01

348

Cardiac involvement in Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ): electrocardiographic, echocardiographic, and morphologic studies  

Microsoft Academic Search

BACKGROUND: Cardiac mortality in Duchenne muscular dystrophy (DMD) has recently become important, because risk of respiratory failure has been reduced due to widespread use of the respirator. The cardiac involvement is characterized by distinctive electrocardiographic abnormalities or dilated cardiomyopathy, but the pathogenesis has remained obscure. In research on DMD, Golden retriever-based muscular dystrophy (GRMD) has attracted much attention as an

Naoko Yugeta; Nobuyuki Urasawa; Yoko Fujii; Madoka Yoshimura; Katsutoshi Yuasa; Michiko R Wada; Masao Nakura; Yoshiki Shimatsu; Masayuki Tomohiro; Akio Takahashi; Noboru Machida; Yoshito Wakao; Akinori Nakamura; Shin'ichi Takeda

2006-01-01

349

The postoperative cardiovascular arrest of a 5-year-old male: an initial presentation of Duchenne's muscular dystrophy.  

PubMed

Anesthesia may be administered to patients with Duchenne's muscular dystrophy, but cases are reported in which apparently healthy children suffer hyperkalemic cardiac arrest. We present the case of a 5-year-old boy whose muscular dystrophy was discovered following a fatal, perioperative cardiac arrest in the postanesthesia care unit. PMID:16430414

Girshin, Michael; Mukherjee, Jana; Clowney, Ross; Singer, Lewis P; Wasnick, John

2006-02-01

350

AAV6-mediated Systemic shRNA Delivery Reverses Disease in a Mouse Model of Facioscapulohumeral Muscular Dystrophy  

Microsoft Academic Search

Treatment of dominantly inherited muscle disorders remains a difficult task considering the need to eliminate the pathogenic gene product in a body-wide fashion. We show here that it is possible to reverse dominant muscle disease in a mouse model of facioscapulohumeral muscular dystrophy (FSHD). FSHD is a common form of muscular dystrophy associated with a complex cascade of epigenetic events

Sergia Bortolanza; Alessandro Nonis; Francesca Sanvito; Simona Maciotta; Giovanni Sitia; Jessica Wei; Yvan Torrente; Clelia Di Serio; Joel R Chamberlain; Davide Gabellini

2011-01-01

351

Becker muscular dystrophy patients with deletions around exon 51; a promising outlook for exon skipping therapy in Duchenne patients  

Microsoft Academic Search

Theoretically, 13% of patients with Duchenne muscular dystrophy may benefit from antisense-mediated skipping of exon 51 to restore the reading frame, which results in the production of a shortened dystrophin protein. We give a detailed description with longitudinal follow up of three patients with Becker muscular dystrophy with in-frame deletions in the DMD gene encompassing exon 51. Their internally deleted,

A. T. J. M. Helderman-van den Enden; C. S. M. Straathof; A. Aartsma-Rus; J. T. den Dunnen; B. M. Verbist; E. Bakker; J. J. G. M. Verschuuren; H. B. Ginjaar

2010-01-01

352

Detection of partial deletion and partial duplication of dystrophin gene in Japanese patients with Duchenne or Becker muscular dystrophy  

Microsoft Academic Search

Summary The dystrophin gene was analyzed in 59 Japanese patients with Duchenne muscular dystrophy (DMD) from 48 unrelated families, including 11 pairs of siblings, and three patients with Becker muscular dystrophy (BMD) from two unrelated families, including one pair of siblings. The relationship between the type of gene abnormality and clinical symptoms was examined. Twenty-seven of 50 (54.0%) unrelated DMD

Keiko Hiyama; Mieko Kodaira; Chiyoko Satoh; Takenori Karakawa; Hitoshi Kameo; Michio Yamakido

1993-01-01

353

Gait assessment in children with duchenne muscular dystrophy during long-distance walking.  

PubMed

The aim of this study was to investigate the alteration of the gait pattern in 25 children with Duchenne muscular dystrophy, using body-worn inertial sensors during a long walking distance. Normalized spatiotemporal gait parameters and their variability were extracted from the angular velocity of the shanks; the smoothness of the trunk movement was assessed based on the spectral entropy of the acceleration norm. As compared to healthy children, patients with Duchenne muscular dystrophy showed significantly lower stride velocity and a less smooth trunk movement. When the group of patients was divided into mild and moderate based on the Motor Function Measure, the authors noticed significantly higher values both for cadence and stride velocity, as well as improved trunk smoothness in the mild versus moderate group. The potential of such parameters to distinguish between different disease states opens new perspectives for the objective assessment of efficacy of the new therapies associated with Duchenne muscular dystrophy. PMID:21765150

Ganea, Raluca; Jeannet, Pierre-Yves; Paraschiv-Ionescu, Anisoara; Goemans, Nathalie M; Piot, Christine; Van den Hauwe, Marleen; Aminian, Kamiar

2011-07-15

354

Cardiac and Pulmonary Function Variability in Duchenne/Becker Muscular Dystrophy: An Initial Report  

PubMed Central

The Duchenne and Becker forms of muscular dystrophy are associated with dilated cardiomyopathy and are diseases in which pulmonary function peaks, then progressively declines. In this report, we quantify cardiopulmonary function variability among brothers. Brothers in 3 of 7 eligible sibships had discordant pulmonary function, with significant differences between the brothers' peak forced vital capacities and their vital capacities at last comparable age. There was no relationship between pulmonary and cardiac function among the siblings. We concluded that despite identical genetic mutations, cardiac and pulmonary function variability was common among brothers in our clinic with Duchenne or Becker muscular dystrophy. If confirmed by larger studies, these results have negative implications for use of genetic testing to predict cardiopulmonary course and response to therapies in Duchenne or Becker muscular dystrophy.

Birnkrant, David J.; Ashwath, Mahi Lakshmi; Noritz, Garey H.; Merrill, Michelle C.; Shah, Tushar A.; Crowe, Carol A.; Bahler, Robert C.

2013-01-01

355

Duchenne and Becker muscular dystrophies: an Indian update on genetics and rehabilitation.  

PubMed

The application of molecular diagnostic techniques has greatly improved the diagnosis, carrier detection, prenatal testing and genetic counseling for families with Duchenne and Becker muscular dystrophy (D/BMD) in India. The prediction of Duchenne muscular dystrophy (DMD) patients to have out-framed deletions and Becker's muscular dystrophy (BMD) patients to have in-frame deletions of dystrophin gene holds well in the vast majority of cases. Mutation detection is obviously critical for diagnosis but it may also be important for future therapeutic purposes. These factors underscore the need for earlier referral, genetic counseling and provision of support and rehabilitation services which are the main priorities for psychosocial assessment and intervention at medical and social levels. PMID:18974550

Nadkarni, Jayshree J; Dastur, Rashna S; Viswanathan, V; Gaitonde, Pradnya S; Khadilkar, Satish V

356

Presence of mechanical dyssynchrony in duchenne muscular dystrophy  

PubMed Central

Background Cardiac dysfunction in boys with Duchenne muscular dystrophy (DMD) is a leading cause of death. Cardiac resynchronization therapy (CRT) has been shown to dramatically decrease mortality in eligible adult population with congestive heart failure. We hypothesized that mechanical dyssynchrony is present in DMD patients and that cardiovascular magnetic resonance (CMR) may predict CRT efficacy. Methods DMD patients (n = 236) were stratified into 4 groups based on age, diagnosis of DMD, left ventricular (LV) ejection fraction (EF), and presence of myocardial fibrosis defined as positive late gadolinum enhancement (LGE) compared to normal controls (n = 77). Dyssynchrony indices were calculated based on timing of CMR derived circumferential strain (ecc). The calculated indices included cross-correlation delay (XCD), uniformity of strain (US), regional vector of variance (RVV), time to maximum strain (TTMS) and standard deviation (SD) of TTMS. Abnormal XCD value was defined as > normal + 2SD. US, RVV, TTMS and SD were calculated for patients with abnormal XCD. Results There was overall low prevalence of circumferential dyssynchrony in the entire DMD population; it increased to 17.1% for patients with abnormal EF and to 31.2% in the most advanced stage (abnormal EF with fibrosis). All but one DMD patient with mechanical dyssynchrony exhibited normal QRS duration suggesting absence of electrical dyssynchrony. The calculated US and RVV values (0.91 ± 0.09, 1.34 ± 0.48) indicate disperse rather than clustered dyssynchrony. Conclusion Mechanical dyssynchrony is frequent in boys with end stage DMD-associated cardiac dysfunction. It is associated with normal QRS complex as well as extensive lateral fibrosis. Based on these findings, it is unlikely that this patient population will benefit from CRT.

2011-01-01

357

Cardiac assessment of patients with late stage Duchenne muscular dystrophy.  

PubMed

Background. Duchenne muscular dystrophy (DMD) patients used to die mainly from pulmonary problems. However, as advances in respiratory care increase life expectancy, mortality due to cardiomyopathy rises. Echocardiography remains the standard diagnostic modality for cardiomyopathy in DMD patients, but is hampered by scoliosis and poor echocardiographic acoustic windows in adult DMD patients. Multigated cardiac radionuclide ventriculography (MUGA) does not suffer from these limitations. N-terminal proBNP (NTproBNP) has shown to be a diagnostic factor for heart failure. We present our initial experience with plasma NT-proBNP measurement in the routine screening and diagnosis of cardiomyopathy in adult mechanically ventilated DMD patients.Methods. Retrospective study, 13 patients. Echocardiography classified left ventricular (LV) function as preserved or depressed. NT-proBNP was determined using immunoassay. LV ejection fraction (LVEF) was determined using MUGA.Results. Median (range) NT-proBNP was 73 (25 to 463) ng/l. Six patients had an NT-proBNP >125 ng/l. Seven patients showed an LVEF <45% on MUGA. DMD patients with depressed LV function (n=4) as assessed by echocardiography had significantly higher median NT-proBNP than those (n=9) with preserved LV function: 346 (266 to 463) ng/l versus 69 (25 to 257) ng/l (p=0.003). NT-proBNP significantly correlated with depressed LV function on echocardiogram and with LVEF determined by MUGA.Conclusion. Although image quality of MUGA is superior to echocardiography, the combination of echocardiography and NT-proBNP achieves similar results in the evaluation of left ventricular function and is less time consuming and burdensome for our patients. We advise to add NT-proBNP to echocardiography in the routine cardiac assessment of DMD patients. (Neth Heart J 2009;17:232-7.). PMID:19789685

van Bockel, E A P; Lind, J S; Zijlstra, J G; Wijkstra, P J; Meijer, P M; van den Berg, M P; Slart, R H J A; Aarts, L P H J; Tulleken, J E

2009-06-01

358

Cardiac assessment of patients with late stage Duchenne muscular dystrophy  

PubMed Central

Background. Duchenne muscular dystrophy (DMD) patients used to die mainly from pulmonary problems. However, as advances in respiratory care increase life expectancy, mortality due to cardiomyopathy rises. Echocardiography remains the standard diagnostic modality for cardiomyopathy in DMD patients, but is hampered by scoliosis and poor echocardiographic acoustic windows in adult DMD patients. Multigated cardiac radionuclide ventriculography (MUGA) does not suffer from these limitations. N-terminal proBNP (NTproBNP) has shown to be a diagnostic factor for heart failure. We present our initial experience with plasma NT-proBNP measurement in the routine screening and diagnosis of cardiomyopathy in adult mechanically ventilated DMD patients. Methods. Retrospective study, 13 patients. Echocardiography classified left ventricular (LV) function as preserved or depressed. NT-proBNP was determined using immunoassay. LV ejection fraction (LVEF) was determined using MUGA. Results. Median (range) NT-proBNP was 73 (25 to 463) ng/l. Six patients had an NT-proBNP >125 ng/l. Seven patients showed an LVEF <45% on MUGA. DMD patients with depressed LV function (n=4) as assessed by echocardiography had significantly higher median NT-proBNP than those (n=9) with preserved LV function: 346 (266 to 463) ng/l versus 69 (25 to 257) ng/l (p=0.003). NT-proBNP significantly correlated with depressed LV function on echocardiogram and with LVEF determined by MUGA. Conclusion. Although image quality of MUGA is superior to echocardiography, the combination of echocardiography and NT-proBNP achieves similar results in the evaluation of left ventricular function and is less time consuming and burdensome for our patients. We advise to add NT-proBNP to echocardiography in the routine cardiac assessment of DMD patients. (Neth Heart J 2009;17:232-7.19789685) PMID:19789685

van Bockel, E.A.P.; Lind, J.S.; Zijlstra, J.G.; Wijkstra, P.J.; Meijer, P.M.; van den Berg, M.P.; Slart, R.H.J.A.; Aarts, L.P.H.J.; Tulleken, J.E.

2009-01-01

359

Importance of lower limb surgery in Duchenne muscular dystrophy.  

PubMed

A total of 123 patients with Duchenne muscular dystrophy (DMD) was surgically treated during two different periods of their course by hip and knee release, aponeurectomy of the iliotibial band and z-shaped Achilles' tendon lengthening. In 57 patients (group I) this was carried out prophylactically as retractions of the lower limb joints were just beginning at the age of 6.4 +/- 1.43 years and in 66 patients (group II) as mild contractures of the joints at the end of walking ability were already manifest with an average age of 9.27 +/- 1.86 years. The average follow-up was 3.7 +/- 1.2 years in both groups. To be able to assess the interindividual course of both groups, we defined "joint and motor quotients", which allowed a complex assessment of joint function and motoric capacity. In addition, both groups were compared with a control group (natural history) consisting of 100 non-operated DMD patients. In both groups a significant release of the contractures could be obtained primarily. Patients in group I showed a much better long-term effect than those in group II. The motor quotient in group I was significantly better over the whole follow-up period (P < 0.001) than in group II or the control group. The prolongation of walking ability by about 2 years compared with the natural history is in our opinion not the central goal of this surgical treatment concept of lower limbs in DMD, but rather the additionally achieved prolongation of an assisted standing ability with the lower limbs free from contractures and deformities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7734231

Forst, R; Forst, J

1995-01-01

360

Problems and potential for gene therapy in Duchenne muscular dystrophy.  

PubMed

Hopes ran high that a cure for Duchenne muscular dystrophy (DMD) would quickly follow the discovery of dystrophin by Lou Kunkel and his group in the 1980's. Myoblast transplantation, the favoured method of gene 'complementation', unfortunately did not progress beyond the experimental stage. A more sober approach to gene therapy followed using a variety of transfection or direct methods to introduce the normal gene. In view of these advances it is timely for the potential of gene therapy for DMD to be considered in the light of the disease process. It may be assumed that if dystrophin is replaced muscle fibre necrosis will cease. For this purpose expression of the gene should be continuous and expressed throughout the body well before there are irreversible changes. It would seem that gene therapy would not be particularly helpful if this occurs when the muscle lesions are near the end stage. If our objective is to retain ambulation dystrophin must be replaced well before the end stage. It should be kept in mind that even when the disorder first becomes clinically apparent at the age of about 5 years, muscle lesions are very advanced in the limb girdle groups. Therefore, the best that may be hoped to achieve by gene therapy at the age of 5 years would be to arrest the process at that stage of involvement with the patient having permanent but static weakness. Cardiac lesions are probably minimal at this time. To improve life expectancy, the respiratory muscles would need to be preserved. The enormous size of the gene is another difficulty so that some thought has been given to the introduction of a 'minigene' converting the clinical phenotype from DMD to the more benign Becker phenotype with improved life expectancy. PMID:9267845

Kakulas, B A

1997-07-01

361

Quality Assurance for Duchenne and Becker Muscular Dystrophy Genetic Testing  

PubMed Central

Duchenne and Becker muscular dystrophies (DMD/BMD) are allelic X-linked recessive disorders that affect approximately 1 in 3500 and 1 in 20,000 male individuals, respectively. Approximately 65% of patients with DMD have deletions, 7% to 10% have duplications, and 25% to 30% have point mutations in one or more of the 79 exons of the dystrophin gene. Most clinical genetics laboratories test for deletions, and some use technologies that can detect smaller mutations and duplications. Reference and quality control materials for DMD/BMD diagnostic and carrier genetic testing are not commercially available. To help address this need, the Centers for Disease Control and Prevention–based Genetic Testing Reference Material Coordination Program, in collaboration with members of the genetic testing and the DMD/BMD patient communities and the Coriell Cell Repositories, have characterized new and existing cell lines to create a comprehensive DMD/BMD reference material panel. Samples from 31 Coriell DMD cell lines from male probands and female carriers were analyzed using the Affymetrix SNP Array 6.0 and Multiplex Ligation-Dependent Probe Amplification (MRC-Holland BV, Amsterdam, the Netherlands), a multiplex PCR assay, and DNA sequence analysis. Identified were 16 cell lines with deletions, 9 with duplications, and 4 with point mutations distributed throughout the dystrophin gene. There were no discordant results within assay limitations. These samples are publicly available from Coriell Institute for Medical Research (Camden, NJ) and can be used for quality assurance, proficiency testing, test development, and research, and should help improve the accuracy of DMD testing.

Kalman, Lisa; Leonard, Jay; Gerry, Norman; Tarleton, Jack; Bridges, Christina; Gastier-Foster, Julie M.; Pyatt, Robert E.; Stonerock, Eileen; Johnson, Monique A.; Richards, C. Sue; Schrijver, Iris; Ma, Tianhui; Miller, Vanessa Rangel; Adadevoh, Yetsa; Furlong, Pat; Beiswanger, Christine; Toji, Lorraine

2011-01-01

362

Verbal and memory skills in males with Duchenne muscular dystrophy  

PubMed Central

Duchenne muscular dystrophy (DMD) is a progressive pediatric disorder that affects both muscle and brain. Children with DMD have mean IQ scores that are about one standard deviation lower than population means, with lower Verbal IQ than Performance IQ scores. For the present study, verbal skills and verbal memory skills were examined in males with DMD with the Clinical Evaluation of Language Fundamentals, 3rd edition, and the California Verbal Learning Test for Children. Performance of 50 males with DMD (age range 6–14y, mean 9y 4mo [SD 2y 1mo]) was compared to normative values. Two subsets of the probands were also compared with two comparison groups: unaffected siblings (n=24; DMD group age range 6–12y, mean 9y 1mo [SD 1y 8mo]; sibling age range 6–15y, mean 9y 11mo [SD 2y 4mo]) and males with cerebral palsy (CP);(n=23; DMD group age range 6–9y, mean 7y 8mo [SD 1y 2mo]; CP age range 6–8y, mean 6y 8mo [SD 0y 8mo]). Results demonstrated that although males with DMD performed slightly more poorly than normative values, they performed comparably to the controls on most measures. Consistent deficits were observed only on tests requiring immediate repetition for verbal material (Recalling Sentences, and Concepts and Directions). On other language tasks, including tests of understanding and use of grammar, and understanding of semantic relationships, the males with DMD performed well. Moreover, the males with DMD performed well on multiple indices of verbal recall, and there was no evidence of declarative memory deficits. DMD is a single-gene disorder that is selectively associated with decreased verbal span capacity, but not impaired recall.

Hinton, V J; Fee, R J; Goldstein, E M; De Vivo, D C

2007-01-01

363

Verbal and memory skills in males with Duchenne muscular dystrophy  

PubMed Central

Duchenne muscular dystrophy (DMD) is a progressive pediatric disorder that affects both muscle and brain. Children with DMD have mean IQ scores that are about one standard deviation lower than population means, with lower Verbal IQ than Performance IQ scores. For the present study, verbal skills and verbal memory skills were examined in males with DMD with the Clinical Evaluation of Language Fundamentals, 3rd edition, and the California Verbal Learning Test for Children. Performance of 50 males with DMD (age range 6–14y, mean 9y 4mo [SD 2y 1mo]) was compared to normative values. Two subsets of the probands were also compared with two comparison groups: unaffected siblings (n=24; DMD group age range 6–12y, mean 9y 1mo [SD 1y 8mo]; sibling age range 6–15y, mean 9y 11mo [SD 2y 4mo]) and males with cerebral palsy (CP); (n=23; DMD group age range 6–9y, mean 7y 8mo [SD 1y 2mo]; CP age range 6–8y, mean 6y 8mo [SD 0y 8mo]). Results demonstrated that although males with DMD performed slightly more poorly than normative values, they performed comparably to the controls on most measures. Consistent deficits were observed only on tests requiring immediate repetition for verbal material (Recalling Sentences, and Concepts and Directions). On other language tasks, including tests of understanding and use of grammar, and understanding of semantic relationships, the males with DMD performed well. Moreover, the males with DMD performed well on multiple indices of verbal recall, and there was no evidence of declarative memory deficits. DMD is a single-gene disorder that is selectively associated with decreased verbal span capacity, but not impaired recall.

Hinton, V J; BA, R J Fee; Goldstein, E M; De Vivo, D C

2007-01-01

364

Evidence for heterogeneity in facioscapulohumeral muscular dystrophy (FSHD)  

SciTech Connect

Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive primary disease of muscle which is usually inherited as an autosomal dominant disorder. FSHD has been localized to the long arm of chromosome 4, specifically to the 4q3.5-qter region. Initially published linkage studies showed no evidence for heterogeneity in FSHD. In the present study the authors have examined individuals in seven FSHD families. Two-point lod scores show significant evidence for linkage for D4S163 (lod score 3.04 at recombination fraction .21) and D4S139 (lod score 3.84 at recombination fraction .20). D4S171 also gave a positive score (lod score 2.56 at recombination fraction .24). Significant evidence for heterogeneity was found for each of the three markers. Multipoint linkage analysis in this region resulted in a peak multipoint lod score of 6.47. The multipoint analysis supported the two-point studies with odds of 20:1 showing linkage and heterogeneity over linkage and homogeneity. Five of the seven families gave a posterior probability of >95% of being of the linked type, while two families appeared unlinked to this region of 4q (P<.01%). Individuals in the two unlinked families met the clinical criteria for the diagnosis of FSHD, including facial weakness, clavicular flattening, scapula winging, proximal muscle weakness, and myopathic changes on muscle biopsies without inflammatory or mitochondrial pathology. This study demonstrates genetic heterogeneity in FSHD and has important implications for both genetic counseling and the elucidation of the etiology of FSHD. 19 refs., 3 figs., 2 tabs.

Gilbert, J.R.; Stajich, J.M.; Wall, S.; Carter, S.C.; Qiu, H.; Vance, J.M.; Stewart, C.S.; Speer, M.C.; Pufky, J.; Yamaoka, L.H.; Rozear, M.; Roses, A.D.; Pericak-Vance, M.A. (Duke Univ. Medical Center, Durham, NC (United States)); Samson, F.; Fardeau, M. (INSERM, Paris (France))

1993-08-01

365

A novel treatment regimen for Duchenne muscular dystrophy.  

PubMed

Duchenne muscular dystrophy (DMD) is the most common, X-linked genetic, skeletal muscle disease, with various regimens of treatment. The objective of this study was to determine the safety and efficacy of a novel treatment regimen for this disease. Thirty boys with DMD were administered prednisone according to the following regimen: in the first year, 1.5 mg/kg/day for the first 3 months, 1.0 mg/kg/day for the next 3 months, 0.75 mg/kg/day for the next 3 months, and 0.5 mg/kg/day for the last 3 months. In the second year, prednisone was administered 0.5 mg/kg on the alternate day for 12 months. The muscle strength (Medical Research Council sum score and Gower's sign), serum enzymes (creatine kinase, creatine kinase isoenzyme-2, and lactate dehydrogenase), pulmonary function (forced vital capacity, maximum voluntary ventilation), body weight, height, and BMI were determined before treatment and 3, 6, 9, 12, and 24 months after treatment. The results showed that the patients' mean Medical Research Council sum score increased from 46.1 at the baseline to 53.6 at 12 months and was maintained at 24 months. Gower's sign disappeared in 22 (73.3%) patients at 12 months and 21 (70.0%) at 24 months. The serum levels of creatine kinase, creatine kinase isoenzyme-2, and lactate dehydrogenase decreased and pulmonary function improved after 24 months of treatment. Significantly increased weight gain, osteoporosis, and cushingoid features were not observed. Our results suggested that this novel prednisone regimen for DMD has similar efficacy and safety as other regimens. PMID:24045777

Li, Mei; Cai, Yunting; Zhong, Min; Zou, Lin; Gong, Caihui

2013-11-13

366

Bethlem myopathy is not allelic to limb-girdle muscular dystrophy type 1A  

SciTech Connect

The Bethlem myopathy, an autosomal-dominant myopathy, shows a distribution of proximal muscle weakness similar to that observed in dominant limb-girdle muscular dystrophy (LGMD). Yet the Bethlem myopathy differs from most limb-girdle dystrophies in two important regards. First, the Bethlem myopathy presents with joint contractures most commonly observed at the elbows, ankles, and neck. Secondly, disease onset in the Bethlem myopathy is in early childhood, while most dominant LGMDs present with adult onset. 6 refs., 1 fig.

Speer, M.C.; Yamaoka, L.H.; Stajich, J.; Lewis, K. [and others

1995-08-28

367

Laminin alpha 2-chain gene mutations in two siblings presenting with limb-girdle muscular dystrophy.  

PubMed

We report two siblings, an 11-year-old boy and his 7-year-old sister, referred to us with a diagnosis of muscular dystrophy. The boy presented at 22 months with delay in walking. A very high serum creatine kinase (CK) level and a dystrophic muscle biopsy lead to a diagnosis of Duchenne muscular dystrophy prior to the identification of the dystrophin gene. Two years later his sister presented with similar problems. A diagnosis of limb-girdle muscular dystrophy was made when they were shown to have inherited different X-chromosomes and normal expression of dystrophin and all sarcoglycans. Their conditions remained static. Recently a slowing of the peripheral motor nerve conduction velocities and T2-weighted brain magnetic resonance imaging showed increased signal of the white matter, both of which are features of merosin-deficient congenital muscular dystrophy. Immunolabelling using a C-terminal laminin alpha 2 chain antibody showed a reduction in expression, while labelling with another antibody that recognises a 300-kDa fragment showed a very significant reduction. Mutational analysis of the LAMA2 gene showed two mutations: one was a G-->C point mutation at position -1 of intron 28 acceptor splicing site. This mutation induced activation of a cryptic splice at nucleotide 4429 of exon 29 and partial skipping of this exon, with conservation of the open reading frame. The other was a nonsense mutation due to a C_T transition at position 5525 of the cDNA sequence (exon 37), resulting in a stop codon. These data confirm that mutations of the LAMA2 gene that do not completely disrupt the production of the protein can give rise to phenotypes considerably milder than classical merosin-deficient congenital muscular dystrophy. Partial laminin alpha 2 deficiency should be considered in the differential diagnosis of limb-girdle muscular dystrophy. PMID:9829280

Naom, I; D'Alessandro, M; Sewry, C A; Philpot, J; Manzur, A Y; Dubowitz, V; Muntoni, F

1998-10-01

368

Clinical and molecular analysis of a large family with three distinct phenotypes of progressive muscular dystrophy.  

PubMed

We describe a unique six-generation, highly consanguineous family originating from an isolated mountainous village in the Russian province of Daghestan. Three separate clinical phenotypes of progressive muscular dystrophy were identified in this large family. Seven patients developed a classical limb-girdle variant of muscular dystrophy (LGMD), with disease onset at 15-30 years and loss of ambulation within a 25-year course. The second group included three patients with a slowly progressive distal myopathy first manifested in the late teens and confined to the tibial and calf muscles. Each of these two phenotypes segregated independently as an autosomal recessive trait, and muscle biopsies showed non-specific myopathic changes. Lastly, two male siblings exhibited an atypical variant of Duchenne muscular dystrophy confirmed by detection of a deletion in the dystrophin gene. To clarify the molecular basis of the polymorphic autosomal recessive form of muscular dystrophy in this kindred, we performed molecular genetic studies on 67 family members and obtained significant evidence for linkage to chromosome 2p. A maximum pairwise lod (logarithm of odds) score of 5.64 was achieved at the zero recombination fraction (i.e. at theta = 0.00) for locus D2S291; multipoint linkage analysis confirmed the most likely location of a mutant gene near D2S291. The patients with LGMD and those with the distal muscular dystrophy phenotype share a common affected homozygous haplotype associated with the same founder chromosome; key recombinants defined D2S286 and D2S292 to be the closest loci flanking the mutant gene. Remarkably, two clinically distinct forms of autosomal recessive muscular dystrophy, LGMD type 2B (LGMD2B) and Miyoshi myopathy, were recently mapped to the same locus. We suggest that all three chromosome 2p-linked conditions may represent allelic disorders, i.e. different phenotypic expressions of a single gene. PMID:9009996

Illarioshkin, S N; Ivanova-Smolenskaya, I A; Tanaka, H; Vereshchagin, N V; Markova, E D; Poleshchuk, V V; Lozhnikova, S M; Sukhorukov, V S; Limborska, S A; Slominsky, P A; Bulayeva, K B; Tsuji, S

1996-12-01

369

Evidence for linkage disequilibrium in chromosome 13-linked Duchenne-like muscular dystrophy  

SciTech Connect

Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive Limb Girdle muscular dystrophy (LGMD2C) characterized by late age of onset, proximal muscle weakness leading to disability, high creatine kinase values, normal intelligence and normal dystrophin in muscle biopsy. We have shown previously that three DLMD families from Tunisia are linked to chromosome 13q12. To further localize the LGMD2C gene, we have investigated seven additional families (119 individuals). Both genotyping and two-point linkage analysis were performed as described elsewhere. 7 refs., 1 fig., 1 tab.

Othmane, K.B.; Speer, M.C.; Stauffer, J. [Duke Univ. Medical Center, Durham, NC (United States)] [and others

1995-09-01

370

Becker muscular dystrophy due to an inversion of exons 23 and 24 of the DMD gene.  

PubMed

The use of hybridization-based methods for Duchenne muscular dystrophy (DMD) mutation analysis is increasingly common. We report a case of Becker muscular dystrophy in which discrepant results between a polymerase chain reaction (PCR)-based single-condition amplification/internal primer (SCAIP) and a comparative genomic hybridization assay incompletely characterized the mutation (an inversion of exons 23 and 24). These results demonstrate the limits of sensitivity and specificity of both tests, and highlight the need for more detailed analysis when intronic deletions are detected by comparative genome hybridization methods. PMID:22006698

Flanigan, Kevin M; Dunn, Diane; Larsen, C Aaron; Medne, Livija; Bönnemann, Carsten B; Weiss, Robert B

2011-11-01

371

Electron Spin Resonance Studies of Erythrocytes from Patients with Myotonic Muscular Dystrophy  

PubMed Central

Electron magnetic resonance experiments have demonstrated that spin-labeled myotonic erythrocyte membranes have spectra that are recognizably different from those of normal erythrocytes. The spin label incorporated in the erythrocyte membranes of patients having myotonic muscular dystrophy is apparently located in a less polar and somewhat more fluid region than the label in a normal membrane. Although the mechanisms of molecular interaction and their relationship to enzymatic differences is unclear, the results lend confirmation to the suggestion that myotonic muscular dystrophy may be a disease resulting from a basic membrane abnormality.

Butterfield, D. A.; Chesnut, D. B.; Roses, A. D.; Appel, S. H.

1974-01-01

372

Gene therapy strategies for Duchenne muscular dystrophy utilizing recombinant adeno-associated virus vectors.  

PubMed

Gene transfer vectors based on adeno-associated virus (AAV) are now widely used in the field of gene therapy. These vectors have been studied for their potential use in treating many diseases, among them the muscular dystrophies, the most common of which is Duchenne muscular dystrophy (DMD). Several recent advances in the areas of AAV serotype analysis, transgene engineering, and vector delivery to muscle, together with novel means of rescuing mutant mRNA transcripts, have yielded impressive results in animal models of DMD. This minireview focuses on these recent advances and their implications for potential treatments for DMD and other neuromuscular disorders. PMID:16361117

Blankinship, Michael J; Gregorevic, Paul; Chamberlain, Jeffrey S

2005-12-19

373

Characteristics of Japanese Duchenne and Becker muscular dystrophy patients in a novel Japanese national registry of muscular dystrophy (Remudy)  

PubMed Central

Background Currently, clinical trials for new therapeutic strategies are being planned for Duchenne and Becker muscular dystrophies (DMD/BMD). However, it is difficult to obtain adequate numbers of patients in clinical trials. As solutions to these problems, patient registries are an important resource worldwide, especially in rare diseases such as DMD/BMD. Methods We developed a national registry of Japanese DMD/BMD patients in collaboration with TREAT-NMD. The registry includes male Japanese DMD/BMD patients whose genetic status has been confirmed by genetic analysis. The registry includes patients throughout Japan. Results As of February 2012, 583 DMD and 105 BMD patients were registered. Most individuals aged less than 20 years. In terms of genetic mutations of registrants of DMD and BMD, deletion of exons was the most frequent (61.4% and 79.0%) followed by point mutations (24.5% and 14.3%) and duplications (13.6% and 4.8%), respectively. 43.6% of DMD are capable of walking, and 76.2% of BMD registrants are able to walk. 41.1% of DMD registrants in the database were treated using steroids. 29.5% of DMD and 23.8% of BMD registrants were prescribed one cardiac medicine at least. 22% of DMD used ventilator support, and non-invasive support was common. Small numbers of DMD and BMD registrants, only 3.9% and 1.0% of them, have received scoliosis surgery. 57 (9.8%) patients were eligible to clinical trial focused on ‘skipping’ exon 51. Conclusions The Remudy has already demonstrated utility in clinical researches and standardization of patients care for DMD/BMD. This new DMD/BMD patient registry facilitates the synchronization of clinical drug development in Japan with that in other countries.

2013-01-01

374

Analysis of Genetic Variations of Lamin A\\/C Gene (LMNA) by Denaturing High-Performance Liquid Chromatography  

Microsoft Academic Search

The human LMNA gene, when mutated, has been shown to cause at least 7 human diseases: dilated cardiomyopathy, Emery Dreifuss muscular dystrophy, limb girdle muscular dystrophy, familial partial lipodystrophy, Charcot Marie tooth disease type II, mandibuloacral dysplasia, and Hutchinson-Gilford Progeria (OMIM #176670). This article describes a high-throughput method for screening the human lamin A\\/C (LMNA) gene for genetic mutations and

Matthew R. G. Taylor; Misi L. Robinson; Luisa Mestroni

2004-01-01

375

The Congenital and Limb-Girdle Muscular Dystrophies: Sharpening the Focus, Blurring the Boundaries  

Microsoft Academic Search

uring the past decade, outstanding progress in the areas of congenital and limb- girdle muscular dystrophies has led to staggering clinical and genetic complexity. With the identification of an increasing number of genetic defects, individual enti- ties have come into sharper focus and new pathogenic mechanisms for muscular dys- trophies,likedefectsofposttranslationalO-linkedglycosylation,havebeendiscovered.Atthesame time, this progress blurs the traditional boundaries between the categories

Janbernd Kirschner; Carsten G. Bonnemann

2004-01-01

376

Androgen Response to Hypothalamic-Pituitary-Adrenal Stimulation with Naloxone in Women with Myotonic Muscular Dystrophy  

Microsoft Academic Search

Myotonic muscular dystrophy (MMD) is a disease of autosomal dominant inheritance characterized by multisystem disease, includ- ing myotonia, muscle-wasting and weakness of all muscular tissues, and endocrine abnormalities attributed to a genetic abnormality causing a defective cAMP-dependent kinase. We have previously re- ported that MMD patients demonstrate ACTH hypersecretion after endogenous CRH release stimulated by naloxone administration while manifesting a

R. P. Buyalos; R. V. JACKSON; G. I. GRICE; G. I. HOCKINGS; D. J. TORPY

1998-01-01

377

Mutations that disrupt the carboxyl-terminus of ?-sarcoglycan cause muscular dystrophy  

Microsoft Academic Search

Recently, mutations in the genes encoding several of the dystrophin-associated proteins have been identi- fied that produce phenotypes ranging from severe Duchenne-like autosomal recessive muscular dystrophy to the milder limb-girdle muscular dys- trophies (LGMDs). LGMD type 2C is generally asso- ciated with a more severe clinical course and is prevalent in northern Africa. A previous study identified a single base

Elizabeth M. McNally; David Duggan; J. Rafael Gorospe; Carsten G. Bönnemann; Marina Fanin; Elena Pegoraro; Hart G. W. Lidov; Satoru Noguchi; Eijiro Ozawa; Richard S. Finkel; Robert P. Cruse; Corrado Angelini; Louis M. Kunkel; Eric P. Hoffman

1996-01-01

378

Gene Expression Profiling in Limb-Girdle Muscular Dystrophy 2A  

Microsoft Academic Search

Limb-girdle muscular dystrophy type 2A (LGMD2A) is a recessive genetic disorder caused by mutations in calpain 3 (CAPN3). Calpain 3 plays different roles in muscular cells, but little is known about its functions or in vivo substrates. The aim of this study was to identify the genes showing an altered expression in LGMD2A patients and the possible pathways they are

Amets Sáenz; Margarita Azpitarte; Rubén Armañanzas; Ainhoa Alzualde; Iñaki Inza; Federico García-Bragado; Gaspar de La Herran; Julián Corcuera; Ana Cabello; Carmen Navarro; Carolina de La Torre; Eduard Gallardo; Isabel Illa; Adolfo López de Munain; Antoni L. Andreu

2008-01-01

379

Modulation of myoblast fusion by caveolin-3 in dystrophic skeletal muscle cells: implications for Duchenne muscular dystrophy and limb-girdle muscular dystrophy-1C.  

PubMed

Caveolae are vesicular invaginations of the plasma membrane. Caveolin-3 is the principal structural component of caveolae in skeletal muscle cells in vivo. We have recently generated caveolin-3 transgenic mice and demonstrated that overexpression of wild-type caveolin-3 in skeletal muscle fibers is sufficient to induce a Duchenne-like muscular dystrophy phenotype. In addition, we have shown that caveolin-3 null mice display mild muscle fiber degeneration and T-tubule system abnormalities. These data are consistent with the mild phenotype observed in Limb-girdle muscular dystrophy-1C (LGMD-1C) in humans, characterized by a approximately 95% reduction of caveolin-3 expression. Thus, caveolin-3 transgenic and null mice represent valid mouse models to study Duchenne muscular dystrophy (DMD) and LGMD-1C, respectively, in humans. Here, we derived conditionally immortalized precursor skeletal muscle cells from caveolin-3 transgenic and null mice. We show that overexpression of caveolin-3 inhibits myoblast fusion to multinucleated myotubes and lack of caveolin-3 enhances the fusion process. M-cadherin and microtubules have been proposed to mediate the fusion of myoblasts to myotubes. Interestingly, we show that M-cadherin is downregulated in caveolin-3 transgenic cells and upregulated in caveolin-3 null cells. For the first time, variations of M-cadherin expression have been linked to a muscular dystrophy phenotype. In addition, we demonstrate that microtubules are disorganized in caveolin-3 null myotubes, indicating the importance of the cytoskeleton network in mediating the phenotype observed in these cells. Taken together, these results propose caveolin-3 as a key player in myoblast fusion and suggest that defects of the fusion process may represent additional molecular mechanisms underlying the pathogenesis of DMD and LGMD-1C in humans. PMID:14517320

Volonte, Daniela; Peoples, Aaron J; Galbiati, Ferruccio

2003-08-07

380

Modulation of Myoblast Fusion by Caveolin-3 in Dystrophic Skeletal Muscle Cells: Implications for Duchenne Muscular Dystrophy and Limb-Girdle Muscular Dystrophy-1C  

PubMed Central

Caveolae are vesicular invaginations of the plasma membrane. Caveolin-3 is the principal structural component of caveolae in skeletal muscle cells in vivo. We have recently generated caveolin-3 transgenic mice and demonstrated that overexpression of wild-type caveolin-3 in skeletal muscle fibers is sufficient to induce a Duchenne-like muscular dystrophy phenotype. In addition, we have shown that caveolin-3 null mice display mild muscle fiber degeneration and T-tubule system abnormalities. These data are consistent with the mild phenotype observed in Limb-girdle muscular dystrophy-1C (LGMD-1C) in humans, characterized by a ?95% reduction of caveolin-3 expression. Thus, caveolin-3 transgenic and null mice represent valid mouse models to study Duchenne muscular dystrophy (DMD) and LGMD-1C, respectively, in humans. Here, we derived conditionally immortalized precursor skeletal muscle cells from caveolin-3 transgenic and null mice. We show that overexpression of caveolin-3 inhibits myoblast fusion to multinucleated myotubes and lack of caveolin-3 enhances the fusion process. M-cadherin and microtubules have been proposed to mediate the fusion of myoblasts to myotubes. Interestingly, we show that M-cadherin is downregulated in caveolin-3 transgenic cells and upregulated in caveolin-3 null cells. For the first time, variations of M-cadherin expression have been linked to a muscular dystrophy phenotype. In addition, we demonstrate that microtubules are disorganized in caveolin-3 null myotubes, indicating the importance of the cytoskeleton network in mediating the phenotype observed in these cells. Taken together, these results propose caveolin-3 as a key player in myoblast fusion and suggest that defects of the fusion process may represent additional molecular mechanisms underlying the pathogenesis of DMD and LGMD-1C in humans.

Volonte, Daniela; Peoples, Aaron J.; Galbiati, Ferruccio

2003-01-01

381

Modulation of Myoblast Fusion by Caveolin-3 in Dystrophic Skeletal Muscle Cells: Implications for Duchenne Muscular Dystrophy and Limb-Girdle Muscular Dystrophy1C  

Microsoft Academic Search

Caveolae are vesicular invaginations of the plasma membrane. Caveolin-3 is the principal structural component of caveolae in skeletal muscle cells in vivo. We have recently generated caveolin-3 transgenic mice and demonstrated that overexpression of wild-type caveolin-3 in skeletal muscle fibers is sufficient to induce a Duchenne-like muscular dystrophy phenotype. In addition, we have shown that caveolin-3 null mice display mild

Daniela Volonte; Aaron J. Peoples; Ferruccio Galbiati

2003-01-01

382

Calpain 3 gene mutations: genetic and clinico-pathologic findings in limb-girdle muscular dystrophy  

Microsoft Academic Search

Mutations in the calpain 3 gene have been proven to be responsible for limb-girdle muscular dystrophy (LGMD) type 2A. To determine the incidence and genotypes of the calpain 3 (p94) gene mutations in Japanese LGMD patients, we sequenced the gene in 80 patients with clinical characteristics of autosomal recessive or sporadic LGMD. We identified 13 distinct pathogenic mutations in 21

Jonghee Chae; Narihiro Minami; Yuko Jin; Masahiro Nakagawa; Kumiko Murayama; Fumie Igarashi; Ikuya Nonaka

2001-01-01

383

Abnormalities in ?-, ?- and ?-sarcoglycan in patients with limb-girdle muscular dystrophy  

Microsoft Academic Search

We have identified 12 cases from a group of 45 patients with early onset limb-girdle muscular dystrophy (LGMD), who have a deficiency of the 50 kDa dystrophin-associated glycoprotein, ?-sarcoglycan. An additional male sibling of one case was also studied clinically. All 12 patients showed a concomitant, but variable, deficiency of ?-, ?- and ?-sarcoglycan. None of our patients had a

C. A. Sewry; J. Taylor; L. V. B. Anderson; E. Ozawa; R. Pogue; F. Piccolo; K. Bushby; V. Dubowitz; F. Muntoni

1996-01-01

384

Immune responses to dystrophin: implications for gene therapy of Duchenne muscular dystrophy  

Microsoft Academic Search

Introduction of dystrophin by gene transfer into the dystrophic muscles of Duchenne muscular dystrophy (DMD) patients has the possibility of triggering an immune response as many patients will not have been exposed to some (or all) of the epitopes of dystrophin. This could in turn lead to cytotoxic destruction of transfected muscle fibres. We assessed such concerns in the dystrophin-deficient

A Ferrer; K E Wells; D J Wells

2000-01-01

385

Normal growth and regenerating ability of myoblasts from unaffected muscles of facioscapulohumeral muscular dystrophy patients  

Microsoft Academic Search

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by a typical regional distribution, featuring composed patterns of clinically affected and unaffected muscles. No treatment is available for this condition, in which the pathophysiological mechanism is still unknown. Autologous transfer of myoblasts from unaffected to affected territories could be considered as a potential strategy to delay or stop muscle

J-T Vilquin; J-P Marolleau; S Sacconi; I Garcin; M-N Lacassagne; I Robert; B Ternaux; B Bouazza; J Larghero; C Desnuelle

2005-01-01

386

Facioscapulohumeral Muscular Dystrophy Presenting as Shoulder Pain in a Baseball Player  

Microsoft Academic Search

Facioscapulohumeral muscular dystrophy is a commonly occurring myopathy that affects the facial and periscapular musculature. We describe a case in a high school throwing athlete that presented as shoulder pain with throwing a baseball. The patient has begun an intensive physical therapy training program that targets his weak scapular stabilizers as well as altering his throwing mechanics. His symptoms have

Scott Kaar; Dale Hazard; Bruce S. Miller

2005-01-01

387

Molecular deletion patterns in families from southern France with Duchenne\\/Becker muscular dystrophies  

Microsoft Academic Search

We studied 38 unrelated patients from southern France with Duchenne (DMD) or Decker (BMD) muscular dystrophy for intragenic deletions of the DMD\\/ BMD gene. We used both multiplex amplification of selected exons and cDNA probes. Of the 26 (68%) unrelated individuals found to have deletions, 24 (92%) were detected by multiplex polymerase chain reaction. All these deletions have been delineated

Mireille Claustres; Sylvie Tuffery; Marie-Pierre Chevron; Marie-Pierre Jozelon; Patricia Martinez; Bernard Echenne; Jacques Demaille

1991-01-01

388

Rapid and powerful decaplex and dodecaplex PGD protocols for Duchenne muscular dystrophy  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD) is a common childhood lethal X-linked recessive disorder, resulting from deletions, duplications and point mutations in the dystrophin gene. Single-cell protocols for preimplantation genetic diagnosis (PGD) still remain challenging due to the enormous size of the gene and the high risk of intragenic recombination, limitations that often lead to sex determination and selection of female embryos.

A Girardet; C Fernandez; M Claustres

2009-01-01

389

Two Children with Muscular Dystrophies Ascertained Due to Referral for Diagnosis of Autism  

Microsoft Academic Search

We report two children who were referred for diagnostic assessment for autism and were subsequently determined to have a muscular dystrophy (MD). Each child had a history of speech delay and social impairments, but also had motor delays that had not previously been investigated. Both children met diagnostic criteria for autism spectrum disorders on standardized assessment. Each child was hypotonic

Lonnie Zwaigenbaum; Mark Tarnopolsky

2003-01-01

390

Spinal fusion in patients with Duchenne's muscular dystrophy and a low forced vital capacity  

Microsoft Academic Search

Traditionally, spinal fusion has been denied to patients with scoliosis secondary to Duchenne's muscular dystrophy (DMD) when their forced vital capacity (FVC) is less than 30–40% of predicted values (PFVC). The reasons for this decision are a theoretically increased risk of adverse events from a prolonged anaesthetic and extensive surgery. This paper presents a retrospective analysis of 30 patients with

A. Marsh; G. Edge; J. Lehovsky

2003-01-01

391

De novo LMNA mutations cause a new form of congenital muscular dystrophy  

Microsoft Academic Search

Objective: To describe a new entity of congenital muscular dystrophies caused by de novo LMNA mutations. Methods: Fifteen patients presenting with a myopathy of onset in the first year of life were subjected to neurological and genetic evaluation. Histopathological and immunohistochemical analyses were performed for all patients. Results: The 15 patients presented with muscle weakness in the first year of

Susana Quijano-Roy; Blaise Mbieleu; Carsten G. Bönnemann; Pierre-Yves Jeannet; Jaume Colomer; Nigel F. Clarke; Jean-Marie Cuisset; Helen Roper; Linda De Meirleir; Adele D'Amico; Rabah Ben Yaou; Andrés Nascimento; Annie Barois; Laurence Demay; Enrico Bertini; Ana Ferreiro; Caroline A. Sewry; Norma B. Romero; Monique Ryan; Francesco Muntoni; Pascale Guicheney; Pascale Richard; Gisèle Bonne; Brigitte Estournet

2008-01-01

392

Decorin and biglycan expression is differentially altered in several muscular dystrophies  

Microsoft Academic Search

Biglycan and decorin are small extracellular proteoglycans that interact with cytokines, whose activity they may modulate, and with matrix proteins, particularly collagens. To better understand their role in muscle fibrosis, we investigated expression of decorin and biglycan transcripts and protein in muscle of several forms of muscular dystrophy, and also expression of perlecan, an extracellular proteoglycan unrelated to collagen deposition.

Simona Zanotti; Tiziana Negri; Cristina Cappelletti; Pia Bernasconi; Eleonora Canioni; Claudia Di Blasi; Elena Pegoraro; Corrado Angelini; Patrizia Ciscato; Alessandro Prelle; Renato Mantegazza; Lucia Morandi; Marina Mora

2005-01-01

393

Mild congenital muscular dystrophy in two patients with an internally deleted laminin alpha2-chain  

Microsoft Academic Search

Congenital muscular dystrophy (CMD) is a group of clinically and genetically heterogeneous disorders in- herited in an autosomal recessive mode. The ?2-chain of laminin-2 (previously called merosin) has been shown by immunohistochemical and genetic analyses to be implicated in the pathogenesis of the 'classic' form of CMD. In the 'merosin-deficient' subgroup, which represents about half of the cases, more definite

Valérie Allamand; Yoshihide Sunada; Mustafa A. M. Salih; Volker Straub; C. O. Ozo; M. H. S. Al-Turaiki; Maksood Akbar; Timo Kolo; Holly Colognato; Xu Zhang; Lydia M. Sorokin; Peter D. Yurchenco; Karl Tryggvason; Kevin P. Campbell

1997-01-01

394

Germinal mosaicism from grand-paternal origin in a family with Duchenne muscular dystrophy  

Microsoft Academic Search

We have identified a Duchenne muscular dystrophy (DMD) pedigree with an unexpected pattern of inheritance. Using marker restriction fragment length polymorphisms detected by probes that lie within and outside the DMD gene, we could demonstrate that the maternal grandfather has transmitted two distinct types of X chromosomes to his offspring. This original observation may be explained by postulating that the

Mireille Claustres; Paule Kjellberg; Marie Desgeorges; Hélène Bellet; Jacques Demaille

1990-01-01

395

Paternal inheritance or a de novo mutation in a Duchenne Muscular Dystrophy pedigree from South India  

Microsoft Academic Search

A six year old boy presented with classical features of Duchenne Muscular Dystrophy (DMD) and was confirmed by absent dystrophin staining on muscle biopsy. In the paternal line there were 5 affected individuals across two generations with classical DMD. There was no family history of the illness in the maternal line. Molecular genetics analysis by PCR of the exons showed

Meera Purushottam; A. Ram Murthy; G. N. Shubha; N. Gayathri; A. Nalini

2008-01-01

396

Segregation and Sporadic Cases of Duchenne Muscular Dystrophy in the Henan Province, China  

Microsoft Academic Search

In the Henan province, China, the segregation ratio of Duchenne muscular dystrophy, estimated through classical segregation analysis on 103 sibships, is p = 0.462, and the maximum likelihood proportion of sporadic cases is x = 0.264. These figures are in agreement with the results of segregation analysis on 1,800 families from different countries; also, the Henan population shows a slight

Fu Weimin; Guido Barbujani

1990-01-01

397

The genetic status of mothers of isolated cases of Duchenne muscular dystrophy  

Microsoft Academic Search

Classical genetic theory, based on assumed equal mutation rates in males and females, predicts that one-third of all cases of Duchenne muscular dystrophy (DMD) in a generation are born as new mutants to non-carrier mothers. Furthermore, less than half the mothers of apparently isolated cases appear to be carriers on the basis of raised serum creatine kinase levels. We have

M Robinow; A D Roses

1983-01-01

398

Correlation between electroretinogram findings and molecular analysis in the Duchenne muscular dystrophy phenotype  

Microsoft Academic Search

Fifteen consecutive patients with the Duchenne muscular dystrophy (DMD) phenotype were studied. Each patient was asked to undergo an ophthalmic examination, an electroretinogram (ERG), and to donate a blood sample for molecular diagnosis. All 15 patients had a normal ophthalmic examination. Electroretinography was successful in 14\\/15 patients. The ERG tracings were normal in seven patients, abnormal in seven, and unreliable

I De Becker; D C Riddell; J M Dooley; F Tremblay

1994-01-01

399

Merosin-negative congenital muscular dystrophy associated with extensive brain abnormalities  

Microsoft Academic Search

Article abstract-Congenital muscular dystrophies (CMDs) are autosomal recessive, heterogeneous disorders. The most frequent form in the Caucasian population is classic (occidental) CMD, characterized by exclusive muscle involve- ment, although abnormal brain white matter signals are occasionally observed on MRI. Recently, deficiency of merosin, the laminin isoform in skeletal muscle, has been identified in classic CMD patients. In skeletal muscle, merosin

Y. Sunada; T. S. Edgar; B. P. Lotz; R. S. Rust; K. P. Campbell

1995-01-01

400

Severe fascioscapulohumeral muscular dystrophy presenting with Coats’ disease and mental retardation  

Microsoft Academic Search

We describe two Norwegian children with fascioscapulohumeral muscular dystrophy in whom Coats’ disease, deafness, mental retardation and possible epilepsy were the presenting features. The children have a 4q35 deletion giving a small residual repeat fragment that they have inherited from their father who is a mosaic. Fundal changes consistent with bilateral Coats’ disease were found in both children. The rapid

Laurence A. Bindoff; Nanette Mjellem; Kristian Sommerfelt; Bård K. Krossnes; Fiona Roberts; Jørgen Krohn; Randi Skarpaas Tranheim; Irene D. Haggerty

2006-01-01

401

Merosin-positive congenital muscular dystrophy in two siblings with cataract and slight mental retardation  

Microsoft Academic Search

We report on two siblings that have been followed for 14 years, with merosin-positive congenital muscular dystrophy (CMD), cataract, retinitis pigmentosa, dysversion of the optic disc, but no cerebral anomalies, except for microcephaly and slight mental retardation (MR). The younger child had three generalized seizures easily controlled by anticonvulsant therapy. Both children presented hypotonia from birth, delayed psychomotor development, generalized

Umbertina C Reed; Ana Maria C Tsanaclis; Mariz Vainzof; Suely K Marie; Mary S Carvalho; Jaime Roizenblatt; Christiane C Pedreira; Aron Diament; José Antonio Levy

1999-01-01

402

Circadian rhythm and variability of heart rate in Duchenne-type progressive muscular dystrophy  

Microsoft Academic Search

Using 24-hour Holter monitoring and time domain and power spectral measurements, we evaluated the variability or the heart rate and its circadian rhythm in 55 male patients with Duchenne-type progressive muscular dystrophy (DMD) to characterize their autonomic function versus findings in 20 normal controls. Comparisons were also made in patients with mild, moderate, and severe stages of DMD. The percent

Masayuki Yotsukura; Kazuya Sasaki; Eisei Kachi; Akira Sasaki; Tadayuki Ishihara; Kyozo Ishikawa

1995-01-01

403

Deletions in the dystrophin gene: analysis of Duchenne and Becker muscular dystrophy patients in Quebec  

Microsoft Academic Search

We have analyzed patient DNA samples in 77 unrelated Duchenne (DMD) and Becker (BMD) muscular dystrophy families, 73 of which were of French Canadian origin. We show that the frequency (68%) and distribution of deletions within the dystrophin gene was neither random nor unique in this population. We localized 33% of the deletions to the proximal portion of the dystrophin

Louise R. Simard; France Gingras; Nathalie Delvoye; Michel Vanasse; Serge B. Melançon; Damian Labuda

1992-01-01

404

Deletion mutations in Duchenne muscular dystrophy (DMD) in Western Saudi children  

Microsoft Academic Search

Duchenne and Becker muscular dystrophy (DMD and BMD) are caused, in the majority of cases, by deletions in the dystrophin gene (DMD). The disease is an X-linked neuromuscular diseases typically caused by disrupting (DMD) or non-disrupting (BMD) the reading frame in the dystrophin (DMD) gene. In the present study, amplifications of the genomic DNAs of unrelated 15 Saudi DMD males

Mohammed T. Tayeb

2010-01-01

405

ERG phenotype of a dystrophin mutation in heterozygous female carriers of Duchenne muscular dystrophy  

Microsoft Academic Search

PURPOSEMutations in the dystrophin gene result in Duchenne muscular dystrophy (DMD). DMD is associated with an abnormal electroretinogram (ERG) if the mutation disrupts the translation of retinal dystrophin (Dp260). Our aim was to determine if incomplete ERG abnormalities would be associated with heterozygous carriers of dystrophin gene mutations.METHODSGanzfeld ERGs were obtained under scotopic and photopic testing conditions from a family

Kathleen M Fitzgerald; Gerhard W Cibis; Ann Headrick Gettel; Robert Rinaldi; David J Harris; Robert A White

1999-01-01

406

Antisense-induced exon skipping for duplications in Duchenne muscular dystrophy  

Microsoft Academic Search

BACKGROUND: Antisense-mediated exon skipping is currently one of the most promising therapeutic approaches for Duchenne muscular dystrophy (DMD). Using antisense oligonucleotides (AONs) targeting specific exons the DMD reading frame is restored and partially functional dystrophins are produced. Following proof of concept in cultured muscle cells from patients with various deletions and point mutations, we now focus on single and multiple

Annemieke Aartsma-Rus; Anneke AM Janson; Gert-Jan B van Ommen

2007-01-01

407

Rare combination of Becker muscular dystrophy and Klinefelter's syndrome in one patient  

Microsoft Academic Search

Becker muscular dystrophy (BMD) was diagnosed in a male patient with Klinefelter's syndrome (47, XXY karyotype). The BMD was confirmed by (i) immunohistological methods and Western blotting, showing decreased quantity of dystrophin in muscle biopsy specimen and (ii) molecular genetic analysis which demonstrated a homozygous deletion of exons 45–47 within the dystrophin gene on both X-chromosomes. The same deletion was

Omeima Zeitoun; Uwe-Peter Ketelsen; Gerhard Wolff; Clemens R. Müller; Rudolf Korinthenberg

1997-01-01

408

A novel splice site mutation in a Becker muscular dystrophy patient  

Microsoft Academic Search

A Becker muscular dystrophy patient was found to have a single base substitution at the 5' end of intron 54. This single base substitution disrupts the invariant GT dinucleotide within the 5' donor splice site and was shown to cause an out of frame deletion of exon 54 during mRNA processing. This is predicted to produce a truncated dystrophin protein

C Bartolo; A C Papp; P J Snyder; M S Sedra; A H Burghes; C D Hall; J R Mendell; T W Prior

1996-01-01

409

Development and validation of laboratory procedures for preimplantation diagnosis of Duchenne muscular dystrophy  

Microsoft Academic Search

In order to develop and validate methods for the preimplantation diagnosis of Duchenne muscular dystrophy (DMD), we have established and evaluated PCR assays for the analysis of four loci within the DMD gene and for two Y chromosome sequences in single cells. A model system using buccal cells picked from mouthwash samples has been used for an extensive evaluation of

C Holding; D Bentley; R Roberts; M Bobrow; C Mathew

1993-01-01

410

Use of Normal Daughters’ and Sisters’ Creatine Kinase Levels in Estimating Heterozygosity in Duchenne Muscular Dystrophy  

Microsoft Academic Search

A modification is given of the original density function formula of Emery and Morton for estimating heterozygosity in X-linked Duchenne muscular dystrophy. This modification takes into account SCK levels in both normal sisters and normal daughters of a suspected carrier in families where there is only one affected male.Copyright © 1977 S. Karger AG, Basel

Alan E. H. Emery; Susan Holloway

1977-01-01

411

Increased Number of Caveolae and Caveolin-3 Overexpression in Duchenne Muscular Dystrophy  

Microsoft Academic Search

Caveolae are small pockets or invaginations localized at the plasma membrane. Caveolins are the principal protein components of caveolae and play an important structural role in the formation of caveolae membranes. Here, we studied by freeze fracture and immunological techniques the spatial organization of caveolae at the muscle cell plasma membrane and the expression of caveolin-3 in Duchenne muscular dystrophy

Silvia Repetto; Massimo Bado; Paolo Broda; Giuseppe Lucania; Emiliana Masetti; Federica Sotgia; Ilaria Carbone; Antonio Pavan; Eduardo Bonilla; Giuseppe Cordone; Michael P. Lisanti; Carlo Minetti

1999-01-01

412

Contrasting Evolutionary Histories of Two Introns of the Duchenne Muscular Dystrophy Gene, Dmd, in Humans  

Microsoft Academic Search

The Duchenne muscular dystrophy (Dmd) locus lies in a region of the X chromosome that experiences a high rate of recombination and is thus expected to be relatively unaffected by the effects of selection on nearby genes. To provide a picture of nucleotide variability at a high-recombination locus in humans, we sequenced 5.4 kb from two introns of Dmd in

Michael W. Nachman; Susan L. Crowell

2000-01-01

413

Incidence of Duchenne muscular dystrophy in New South Wales and Australian Capital Territory  

Microsoft Academic Search

A survey was conducted during 1977 to 1978 to determine the incidence of Duchenne muscular dystrophy in New South Wales and the Australian Capital Territory. Ninety-nine cases born between 1960 and 1971 were ascertained representing an incidence rate of 18.6 per 100 000 liveborn males. Over 60% of the ascertained males were isolated cases, and only 7% of affected males

J Cowan; J Macdessi; A Stark; G Morgan

1980-01-01

414

Germinal mosaicism increases the recurrence risk for 'new' Duchenne muscular dystrophy mutations  

Microsoft Academic Search

In 288 Dutch and Belgian Duchenne and Becker muscular dystrophy families, the parental origin of 41 new deletion or duplication mutations was determined. Twenty seven of the new mutations occurred in the maternal X chromosome and nine in the grandmaternal and five in the grandpaternal X chromosome. The grandparental data are compatible with equal mutation rates for DMD in male

E Bakker; H Veenema; J T Den Dunnen; C van Broeckhoven; P M Grootscholten; E J Bonten; G J van Ommen; P L Pearson

1989-01-01

415

A standardized method for the evaluation of respiratory muscle endurance in patients with Duchenne muscular dystrophy  

Microsoft Academic Search

The aim of the study was to develop a standardized method using controlled breathing to quantify respiratory muscle endurance in children with Duchenne muscular dystrophy (DMD) and to test its reproducibility. In 10 DMD patients, all between 10 and 14 years (mean age, 11.5±1.5 years), except for two patients of 20 and 22 years, and 10 healthy children (mean age,

Stefan Matecki; Nathalie Topin; Maurice Hayot; François Rivier; Bernard Echenne; Christian Prefaut; Michele Ramonatxo

2001-01-01

416

Parents' Perspectives on Coping with Duchenne Muscular Dystrophy and Concomitant Specific Learning Disabilities  

ERIC Educational Resources Information Center

|This study addresses parental perspectives and coping strategies related to Duchenne muscular dystrophy and specific learning disabilities. Data were collected through individual semi-structured in-depth interviews with fifteen sets of parents. Participants were selected based on variables such as age of children, number of children with both…

Webb, Carol L.

2005-01-01

417

Increased myofibrillar protein catabolism in Duchenne muscular dystrophy measured by 3-methylhistidine excretion in the urine  

Microsoft Academic Search

Myofibrillar protein catabolic rate was calculated in seven patients with Duchenne muscular dystrophy from the amount of 3-methylhistidine excreted in the urine, and found to be over three times that found in a control series when expresses as the percentage of myofibrillar protein catabolised per day. It is suggested that measurement of myofibrillar protein catabolic rate may add a useful

R O McKeran; D Halliday; P Purkiss

1977-01-01

418

Long-range restriction map around the Duchenne muscular dystrophy gene  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD, reviewed in ref. 1) is an X-linked recessive disease affecting about 1 in 4,000 newborn boys. As in many other inherited diseases, the biochemical basis of the condition is unkown, and as yet there is no effective treatment. Translocations, deletions and other mutations leading to the DMD phenotype are distributed over a chromosomal area of large,

Margit Burmeister; Hans Lehrach

1986-01-01

419

Conservation of the Duchenne muscular dystrophy gene in mice and humans  

Microsoft Academic Search

A portion of the Duchenne muscular dystrophy (DMD) gene transcript from human fetal skeletal muscle and mouse adult heart was sequence, representing approximately 25 percent of the total, 14-kb DMD transcript. The nucleic acid and predicted amino acid sequences from the two species are nearly 90 percent homologous. The amino acid sequence that is predicted from this portion of the

E. P. Hoffman; A. P. Monaco; C. C. Feener; L. M. Kunkel

1987-01-01

420

Evaluation of Narrative Abilities in Patients Suffering from Duchenne Muscular Dystrophy  

ERIC Educational Resources Information Center

|The present work investigated cognitive, linguistic and narrative abilities in a group of children suffering from Duchenne Muscular Dystrophy, an allelic X-linked recessive disorder caused by mutations in the gene encoding dystrophin. The patients showed mildly reduced IQ with lower Verbal than Performance Intelligence Quotient and were mildly…

Marini, A.; Lorusso, M. L.; D'Angelo, M. G.; Civati, F.; Turconi, A. C.; Fabbro, F.; Bresolin, N.

2007-01-01

421

Dystrophin Expression in Myofibers of Duchenne Muscular Dystrophy Patients Following Intramuscular Injections of Normal Myogenic Cells  

Microsoft Academic Search

Three Duchenne muscular dystrophy (DMD) patients received injections of myogenic cells obtained from skeletal muscle biopsies of normal donors. The cells (30 × 106) were injected in 1 cm3 of the tibialis anterior by 25 parallel injections. We performed similar patterns of saline injections in the contralateral muscles as controls. The patients received tacrolimus for immunosuppression. Muscle biopsies were performed

Daniel Skuk; Brigitte Roy; Marlyne Goulet; Pierre Chapdelaine; Jean-Pierre Bouchard; Raynald Roy; Francine J. Dugré; Jean-Guy Lachance; Louise Deschênes; Hélène Senay; Michel Sylvain; Jacques P. Tremblay

2004-01-01

422

Intracellular calcium and pathogenesis and antenatal diagnosis of Duchenne muscular dystrophy  

Microsoft Academic Search

One of the earliest and most important abnormalities of fetal muscle in Duchenne muscular dystrophy is an increase in eosinophilic fibres (those that stain darkly with eosin). A study of normal and at-risk male fetuses after abortion was carried out, which showed that these eosinophilic fibres contain increased intracellular calcium, which suggests that this is an early biochemical change in

A E Emery; D Burt

1980-01-01

423

Correlation of muscle fiber type measurements with clinical and molecular genetic data in Duchenne muscular dystrophy  

Microsoft Academic Search

Clinical improvement following surgery in patients with Duchenne muscular dystrophy (DMD) may be influenced by the severity of muscle fiber damage. This study correlates morphometric alterations of muscle fiber types, severity of fat tissue proliferation and fibrosis with Western blots, multiplex polymerase chain reaction (PCR), and postoperative state in DMD. The main results of this study show that the mean

Jian-Feng Wang; Jürgen Forst; Sebastian Schröder; J. Michael Schröder

1999-01-01

424

Mild and severe muscular dystrophy caused by a single {gamma}-sarcoglycan mutation  

SciTech Connect

Autosomal recessive muscular dystrophy is genetically heterogeneous. One form of this disorder, limb-girdle muscular dystrophy type 2C (LGMD 2C), is prevalent in northern Africa and has been shown to be associated with a single mutation in the gene encoding the dystrophin-associated protein {gamma}-sarcoglycan. The previous mutation analysis of {gamma}-sarcoglycan required the availability of muscle biopsies. To establish a mutation assay for genomic DNA, the intron-exon structure of the {gamma}-sarcoglycan gene was determined, and primers were designed to amplify each of the exons encoding {gamma}-sarcoglycan. We studied a group of Brazilian muscular dystrophy patients for mutations in the {gamma}-sarcoglycan gene. These patients were selected on the basis of autosomal inheritance and/or the presence of normal dystrophin and/or deficiency of {alpha}-sarcoglycan immunostaining. Four of 19 patients surveyed had a single, homozygous mutation in the {gamma}-sarcoglycan gene. The mutation identified in these patients, all of African-Brazilian descent, is identical to that seen in the North African population, suggesting that even patients of remote African descent may carry this mutation. The phenotype in these patients varied considerably. Of four families with an identical mutation, three have a severe Duchenne-like muscular dystrophy. However, one family has much milder symptoms, suggesting that other loci may be present that modify the severity of the clinical course resulting from {gamma}-sarcoglycan gene mutations. 19 refs., 5 figs., 3 tabs.

McNally, E.M.; Boennemann, C.G.; Lidov, H.G.W. [Brigham and Women`s Hospital, Boston, MA (United States)] [and others

1996-11-01

425

Clinical phenotype in congenital muscular dystrophy: correlation with expression of merosin in skeletal  

Microsoft Academic Search

It has recently been shown that merosin, an extracellular matrix protein linked to the dystrophin-associated glycoproteins, is deficient in a proportion of patients with classical congenital muscular dystrophy (CMD). We have undertaken a detailed study of the clinical features and brain imaging in 24 cases of CMD in relation to the merosin status.Immunocytochemistry showed that merosin was present in 13

J. Philpot; C. Sewry; J. Pennock; V. Dubowitz

1995-01-01

426

Skeletal and Cardiac Myopathies in Mice Lacking Utrophin and Dystrophin: A Model for Duchenne Muscular Dystrophy  

Microsoft Academic Search

Dystrophin is a cytoskeletal protein of muscle fibers; its loss in humans leads to Duchenne muscular dystrophy, an inevitably fatal wasting of skeletal and cardiac muscle. mdx mice also lack dystrophin, but are only mildly dystrophic. Utrophin, a homolog of dystrophin, is confined to the postsynaptic membrane at skeletal neuromuscular junctions and has been implicated in synaptic development. However, mice

R. Mark Grady; Haibing Teng; Mia C Nichol; Jeanette C Cunningham; Robert S Wilkinson; Joshua R Sanes

1997-01-01

427

Modular flexibility of dystrophin: Implications for gene therapy of Duchenne muscular dystrophy  

Microsoft Academic Search

Attempts to develop gene therapy for Duchenne muscular dystrophy (DMD) have been complicated by the enormous size of the dystrophin gene. We have performed a detailed functional analysis of dystrophin structural domains and show that multiple regions of the protein can be deleted in various combinations to generate highly functional mini- and micro-dystrophins. Studies in transgenic mdx mice, a model

Scott Q. Harper; Michael A. Hauser; Christiana DelloRusso; Dongsheng Duan; Robert W. Crawford; Stephanie F. Phelps; Hollie A. Harper; Ann S. Robinson; John F. Engelhardt; Susan V. Brooks; Jeffrey S. Chamberlain

2002-01-01

428

Teaching NeuroImages: Characteristic phenotype of Ullrich congenital muscular dystrophy.  

PubMed

A 21-year-old woman presented with clinically classic signs of Ullrich congenital muscular dystrophy(1) (figure). Genetic testing of collagen VI genes revealed a homozygous mutation c.2329T>C, p.Cys777Arg in the COL6A2 gene, consistent with the clinical diagnosis. PMID:23940025

Liew, Wendy K M; Darras, Basil T

2013-08-13

429

Animal Models for Muscular Dystrophy Show Different Patterns of Sarcolemmal Disruption  

Microsoft Academic Search

Genetic defects in a number of components of the dystrophin-glycoprotein complex (DGC) lead to distinct forms of muscular dystrophy. However, little is known about how alterations in the DGC are mani- fested in the pathophysiology present in dystrophic muscle tissue. One hypothesis is that the DGC protects the sarcolemma from contraction-induced damage. Us- ing tracer molecules, we compared sarcolemmal integ-

Volker Straub; Jill A. Rafael; Jeffrey S. Chamberlain; Kevin P. Campbell

1997-01-01

430

Duchenne and Becker muscular dystrophy: contribution of a molecular and immunohistochemical analysis in diagnosis in Morocco.  

PubMed

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders caused by mutations of the DMD gene located at Xp21. In DMD patients, dystrophin is virtually absent; whereas BMD patients have 10% to 40% of the normal amount. Deletions in the dystrophin gene represent 65% of mutations in DMD/BMD patients. To explain the contribution of immunohistochemical and genetic analysis in the diagnosis of these dystrophies, we present 10 cases of DMD/BMD with particular features. We have analyzed the patients with immunohistochemical staining and PCR multiplex to screen for exons deletions. Determination of the quantity and distribution of dystrophin by immunohistochemical staining can confirm the presence of dystrophinopathy and allows differentiation between DMD and BMD, but dystrophin staining is not always conclusive in BMD. Therefore, only identification involved mutation by genetic analysis can establish a correct diagnosis. PMID:19461958

Bellayou, Hanane; Hamzi, Khalil; Rafai, Mohamed Abdou; Karkouri, Mehdi; Slassi, Ilham; Azeddoug, Houssine; Nadifi, Sellama

2009-05-19

431

?7?1 Integrin Does Not Alleviate Disease in a Mouse Model of Limb Girdle Muscular Dystrophy Type 2F  

PubMed Central

Transgenic expression of the ?7?1 integrin in the dystrophic mdx/utr?/? mouse decreases development of muscular dystrophy and enhances longevity. To explore the possibility that elevating ?7?1 integrin expression could also ameliorate different forms of muscular dystrophy, we used transgenic technology to enhance integrin expression in mice lacking ?-sarcoglycan (? sgc), a mouse model for human limb girdle muscular dystrophy type 2F. Unlike ?7 transgenic mdx/utr?/? mice, enhanced ?7?1 integrin expression in the ? sgc-null mouse did not alleviate muscular dystrophy in these animals. Expression of the transgene in the ? sgc-null did not alleviate dystrophic histopathology, nor did it decrease cardiomyopathy or restore exercise tolerance. One hallmark of integrin-mediated alleviation of muscular dystrophy in the mdx/utr?/? background is the restoration of myotendinous junction integrity. As assessed by atomic force microscopy, myotendinous junctions from normal and ? sgc-null mice were indistinguishable, thus suggesting the important influence of myotendinous junction integrity on the severity of muscular dystrophy and providing a possible explanation for the inability of enhanced integrin expression to alleviate dystrophy in the ? sgc-null mouse. These results suggest that distinct mechanisms underlie the development of the diseases that arise from deficiencies in dystrophin and sarcoglycan.

Milner, Derek J.; Kaufman, Stephen J.

2007-01-01

432

Immunological identification of a high molecular weight protein as a condidate for the product of the Duchenne muscular dystrophy gene  

SciTech Connect

An oligopeptide was synthesized based on translation of the nucleotide sequence of the putative exon region of clone pERT87-25 from the gene for Duchenne muscular dystrophy. Immunization of rabbits with this oligopeptide induced the formation of antibodies directed against a protein present in human, rat, and rabbit skeletal muscle. This protein, which is missing in the skeletal muscle of two patients with Duchenne muscular dystrophy, has a molecular mass of {approx}320-420 kDa and is clearly different from the putative Duchenne muscular dystrophy-related protein nebulin. The data suggest that this 320-420-kDa protein is produced by the Duchenne muscular dystrophy gene.

Kao, L.; Krstenansky, J.; Mendell, J.; Rammohan, K.W.; Gruenstein, E. (Univ. of Cincinnati College of Medicine, OH (USA))

1988-06-01

433

Decreased mechanical stiffness in LMNA-\\/- cells is caused by defective nucleo-cytoskeletal integrity : implications for the development of laminopathies  

Microsoft Academic Search

Q1 (LMNA ). A prominent feature in several of these diseases is muscle wasting, as seen in Emery-Dreifuss muscle dystrophy, dilated cardiomyopathy and limb-girdle muscular dystrophy. Although the mechanisms underlying this phenotype remain largely obscure, two major working hypotheses are currently being investigated, namely, defects in gene regulation and\\/or abnormalities in nuclear architec- ture causing cellular fragility. In this study,

Jos L. V. Broers; Emiel A. G. Peeters; Helma J. H. Kuijpers; Jorike Endert; Frans C. S. Ramaekers; Cees W. J. Oomens; Frank P. T. Baaijens

2004-01-01

434

[Erythrocyte membrane in Duchenne muscular dystrophy. III. Modifications of acetylcholinesterase].  

PubMed

Membrane-bound acetylcholinesterase was assayed in erythrocyte ghosts from patients with Duchenne Muscular Distrophy and from the members of their family. Modifications was observed both in Km and Vmax, indicating changes in conformations of the enzyme. PMID:7470283

Campagnoli, P; Leporoni, B; Bravi, S; Lenaz, G

1980-12-15

435

A new dysferlin gene mutation in two Japanese families with limb-girdle muscular dystrophy 2B and Miyoshi myopathy  

Microsoft Academic Search

We found a new dysferlin gene mutation in two Japanese families, one with limb-girdle muscular dystrophy 2B and the other with Miyoshi myopathy. All patients in the limb-girdle muscular dystrophy 2B family showed apparent proximal dominant muscle atrophy and weakness, whereas a patient with Miyoshi myopathy in the second family showed distal muscle involvement at an early stage. The common

Hidetsugu Ueyama; Toshihide Kumamoto; Shin-ichiro Nagao; Tomoko Masuda; Hideo Horinouchi; Shin Fujimoto; Tomiyasu Tsuda

2001-01-01

436

Disruption of the ?-Sarcoglycan Gene Reveals Pathogenetic Complexity of Limb-Girdle Muscular Dystrophy Type 2E  

Microsoft Academic Search

Limb-girdle muscular dystrophy type 2E (LGMD 2E) is caused by mutations in the ?-sarcoglycan gene, which is expressed in skeletal, cardiac, and smooth muscle. ?-sarcoglycan-deficient (Sgcb-null) mice developed severe muscular dystrophy and cardiomyopathy with focal areas of necrosis. The sarcoglycan–sarcospan and dystroglycan complexes were disrupted in skeletal, cardiac, and smooth muscle membranes. ?-sarcoglycan was also reduced in membrane preparations of

Madeleine Durbeej; Ronald D. Cohn; Ronald F. Hrstka; Steven A. Moore; Valérie Allamand; Beverly L. Davidson; Roger A. Williamson; Kevin P. Campbell

2000-01-01

437

Effect of Long-term Steroids on Cough Efficiency and Respiratory Muscle Strength in Patients With Duchenne Muscular Dystrophy  

Microsoft Academic Search

OBJECTIVE.The objective of this study was to determine whether long-term steroid therapy is associated with increased peak cough flow in patients with Duchenne muscular dystrophy and to determine which pulmonary function test variable is most predictive of peak cough flow. METHODS.In this case-control study, the medical charts of patients who had Duchenne muscular dystrophy and had pulmonary function tests at

Ameet S. Daftary; Mark Crisanti; Maninder Kalra; Brenda Wong; Raouf Amin

2010-01-01

438

Fukuyama-type congenital muscular dystrophy: the first human disease to be caused by an ancient retrotransposal integration  

Microsoft Academic Search

Fukuyama-type congenital muscular dystrophy (FCMD), one of the most common autosomal recessive disorders in the Japanese population, is characterized by congenital muscular dystrophy in combination with cortical dysgenesis (micropolygyria). Recently we identified on chromosome 9q31 the gene responsible for FCMD, which encodes a novel 461 amino acid protein that we have termed fukutin. Most FCMD-bearing chromosomes (87%) derive from a

Tatsushi Toda; Kazuhiro Kobayashi

1999-01-01

439

Expression of the putative Duchenne muscular dystrophy gene in differentiated myogenic cell cultures and in the brain  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD), a sex-linked degenerative disorder of the muscle, is one of the most common lethal genetic diseases in man. It affects about one male in 3,500, with an estimated one-third of cases being caused by new mutations. A less severe disease, Becker's muscular dystrophy (BMD), maps to the same chromosomal locus and is most probably an allelic

Uri Nudel; Kenneth Robzyk; David Yaffe

1988-01-01

440

Muscular dystrophy in an X; 1 translocation female suggests that Duchenne locus is on X chromosome short arm  

Microsoft Academic Search

A unique combination of a Duchenne-like muscular dystrophy in a girl with a translocation-inversion rearrangement involving an X chromosome and a no 1 chromosome appeared as a result of both gene mutation and chromosome mutation in the mother. The X-autosome rearrangement would permit full expression of an X-linked recessive gene, such as that for Duchenne muscular dystrophy, in a female,

R H Lindenbaum; G Clarke; C Patel; M Moncrieff; J T Hughes

1979-01-01

441

Shifts in macrophage phenotypes and macrophage competition for arginine metabolism affect the severity of muscle pathology in muscular dystrophy  

Microsoft Academic Search

Duchenne muscular dystrophy (DMD) is the most common, lethal, muscle-wasting disease of childhood. Previous investigations have shown that muscle macrophages may play an important role in promoting the pathology in the mdx mouse model of DMD. In the present study, we investigate the mechanism through which macrophages promote mdx dystrophy and assess whether the phenotype of the macrophages changes between

S. Armando Villalta; Hal X. Nguyen; Bo Deng; Tomomi Gotoh; James G. Tidball

2009-01-01

442

NUTRITIONAL MUSCULAR DYSTROPHY IN THE GUINEA PIG AND RABBIT  

PubMed Central

A diet is described, which leads to a progressive, highly selective, and ultimately fatal dystrophy of the voluntary muscles. Guinea pigs and rabbits are susceptible, rats resistant. The diet used is complete in known requirements, except for vitamin E; the addition of this factor, however, does not prevent the development of the disease. The lesions are not due to inanition, infection, or scurvy, and must be referred to some still unknown factor.

Goettsch, Marianne; Pappenheimer, Alwin M.

1931-01-01

443

Wolff-Parkinson-White Syndrome as Initial Manifestation of Becker Muscular Dystrophy  

Microsoft Academic Search

Background:  Cardiac involvement may precede the onset of muscular manifestations in Becker muscular dystrophy (BMD), but Wolff-Parkinson-White\\u000a (WPW) syndrome has not been reported as initial cardiac manifestation of BMD.\\u000a \\u000a \\u000a \\u000a Case Study:  In a 43-year-old, HIV-negative male, WPW syndrome was diagnosed at age 26 years upon a routine surface ECG, carried out for\\u000a recurrent palpitations since childhood. Since then, WPW syndrome was occasionally

Josef Finsterer; Claudia Stöllberger; Stefan Quasthoff

2008-01-01

444

Congenital muscular dystrophy with cerebral white matter hypodensity. Correlation of clinical features and merosin deficiency.  

PubMed

We report clinical and pathological findings in 9 children affected by congenital muscular dystrophy with normal or borderline intelligence and hypodensity of cerebral white matter (CMD-HWM), also frequently called 'occidental or western form of cerebro-muscular dystrophy' (OCMD). Our patients have uniform, distinct, clinical presentation that includes: normal or subnormal intelligence, severe, slowly progressive motor disability, high rate of facial involvement and dysmorphic aspect, increased creatine kinase levels and variable degrees of abnormal, radiographic, cerebral white matter pattern. By comparing our cases with previous reports we suggest that this subtype of CMD is not uncommon in Brazil and it is represented by a particularly severe and homogeneous clinical picture with important motor disability. The immunohistochemical staining for merosin, performed on the muscle biopsy of 6 among 9 patients, showed that all are merosin negative. PMID:8907344

Reed, U C; Marie, S K; Vainzof, M; Salum, P B; Levy, J A; Zatz, M; Diament, A

445

Muscular degeneration in Duchenne's dystrophy may be caused by a mitochondrial defect.  

PubMed

Duchenne's dystrophy (DMD), a recessive chromosome X-related disease, is the most common and severe form of myopathy. The different theories (vascular, neurogenic, membraneous, calcic and auto-immune) formulated to account for this disease have not been swept away by the discovery of the DMD gene and the deficient protein, dystrophin, since the exact cellular role played by the latter is still unknown. Our work on skeletal muscle has demonstrated a mitochondrial deficiency of the calcium-specific protein, calmitine, in degenerating muscle of myopathic persons and animals. Considering its great affinity for calcium, this protein specific to skeletal muscle could be essential to mitochondrial calcium regulation and thus to the functioning of the entire muscle cell. Its deficiency in Duchenne's and Becker type muscular dystrophy could be due to a mitochondrial genome alteration solely accountable for muscular degeneration. This hypothesis challenges the supposedly essential but still undefined role that researchers have attributed to dystrophin. PMID:7666833

Lucas-Heron, B

1995-04-01

446

Merosin-deficient congenital muscular dystrophy. Partial genetic correction in two mouse models.  

PubMed Central

Humans and mice with deficiency of the alpha2 subunit of the basement membrane protein laminin-2/merosin suffer from merosin-deficient congenital muscular dystrophy (MCMD). We have expressed a human laminin alpha2 chain transgene under the regulation of a muscle-specific creatine kinase promoter in mice with complete or partial deficiency of merosin. The transgene restores the synthesis and localization of merosin in skeletal muscle, and greatly improves muscle morphology and integrity and the health and longevity of the mice. However, the transgenic mice share with the nontransgenic dystrophic mice a progressive lameness of hind legs, suggestive of a nerve defect. These results indicate that the absence of merosin in tissues other than the muscle, such as nervous tissue, is a critical component of MCMD. Future gene therapies of human MCMD, and perhaps of other forms of muscular dystrophy, may require restoration of the defective gene product in multiple tissues.

Kuang, W; Xu, H; Vachon, P H; Liu, L; Loechel, F; Wewer, U M; Engvall, E

1998-01-01

447

Progress in muscular dystrophy research with special emphasis on gene therapy  

PubMed Central

Duchenne muscular dystrophy (DMD) is an X-linked, progressive muscle-wasting disease caused by mutations in the DMD gene. Since the disease was described by physicians in the 19th century, information about the subject has been accumulated. One author (Sugita) was one of the coworkers who first reported that the serum creatine kinase (CK) level is elevated in progressive muscular dystrophy patients. Even 50 years after that first report, an elevated serum CK level is still the most useful marker in the diagnosis of DMD, a sensitive index of the state of skeletal muscle, and useful to evaluate therapeutic effects. In the latter half of this article, we describe recent progress in the therapy of DMD, with an emphasis on gene therapies, particularly exon skipping.

SUGITA, Hideo; TAKEDA, Shin'ichi

2010-01-01

448

Candidate-gene testing for orphan limb-girdle muscular dystrophies  

PubMed Central

Summary The term limb-girdle muscular dystrophies (LGMD) identify about two dozens of distinct genetic disorders. Additional genes must play a role, since there are LGMD families excluded from any known locus. The aim of our work is to test a number of candidate genes in unclassified LGMD patient and control DNA samples. We selected the following 11 candidate genes: myozenin 1, 2 and 3), gamma-filamin, kinectin-1, enolase-3 beta, ZASP, TRIM 11 and TRIM 17, OZZ and zeta –sarcoglycan. These candidates were chosen for a combination of different reasons: chromosomal position, sequence homology, interaction properties or muscular dystrophy phenotypes in animal models. The exon and flanking intron sequences were subjected to molecular testing by comparative mutation scanning by HT-DHPLC of LGMD patients versus control. We identified a large number of variations in any of the genes in both patients and controls. Correlations with disease or possible modifying effects on the LGMD phenotype remain to be investigated.

Aurino, S; Piluso, G; Saccone, V; Cacciottolo, M; D'Amico, F; Dionisi, M; Totaro, A; Belsito, A; Di Vicino, U; Nigro, V

2008-01-01

449

Risk assessment and genetic counseling in families with Duchenne muscular dystrophy.  

PubMed

The Duchenne Muscular dystrophy (DMD) is the most frequent muscle disorder in childhood caused by mutations in the Xlinked dystrophin gene (about 65% deletions, about 7% duplications, about 26% point mutations and about 2% unknown mutations). The clinically milder Becker muscular dystrophy (BMD) is allelic to DMD. About 33% of all patients are due to de novo mutations and germ line mosaicism is frequently observed. While in earlier studies equal mutation rates in males and females had been reported, a breakdown by mutation types can better explain the sex ratio of mutations: Point mutations and duplications arise preferentially during spermatogenesis whereas deletions mostly arise in oogenesis. With current analytical methods, the underlying mutation can be identified in the great majority of cases and be used for carrier detection. However, in families with no mutation carrier available, the genetic model to be used for counselling of relatives can be quite complex. PMID:23620649

Grimm, Tiemo; Kress, Wolfram; Meng, Gerhard; Müller, Clemens R

2012-12-01

450

An ex vivo Gene Therapy Approach to Treat Muscular Dystrophy Using inducible Pluripotent Stem Cells  

PubMed Central

Duchenne muscular dystrophy is a progressive and incurable neuromuscular disease caused by genetic and biochemical defects of the dystrophin-glycoprotein complex. Here we show the regenerative potential of myogenic progenitors derived from corrected dystrophic induced pluripotent stem (iPS) cells generated from fibroblasts of mice lacking both dystrophin and utrophin. We correct the phenotype of dystrophic iPS cells using a Sleeping Beauty transposon carrying the micro-utrophin (?UTRN) gene, differentiate these cells into skeletal muscle progenitors, and transplant them back into dystrophic mice. Engrafted muscles displayed large numbers of micro-utrophin-positive myofibers, with biochemically restored dystrophin-glycoprotein complex and improved contractile strength. The transplanted cells seed the satellite cell compartment, responded properly to injury and exhibit neuromuscular synapses. We also detect muscle engraftment after systemic delivery of these corrected progenitors. These results represent an important advance toward the future treatment of muscular dystrophies using genetically corrected autologous iPS cells.

Filareto, Antonio; Parker, Sarah; Darabi, Radbod; Borges, Luciene; Iacovino, Michelina; Schaaf, Tory; Mayerhofer, Timothy; Chamberlain, Jeffrey S; Ervasti, James M.; McIvor, R. Scott; Kyba, Michael; Perlingeiro, Rita C.R.

2013-01-01

451

Diagnostic, predictive, and prenatal testing for facioscapulohumeral muscular dystrophy: diagnostic approach for sporadic and familial cases.  

PubMed Central

Facioscapulohumeral muscular dystrophy (FSHD) is one of the common inherited neuromuscular disorders. The major gene involved, FSHD1, has been localised to chromosome 4q35. This 4q35 locus, detected by pE13-11 (D4F104S1), shows a mutation frequency of about 10% of the incidence. New mutants are characterised by de novo deletions of tens to hundreds of kilobases of DNA. Although these deletion fragments are very useful as a molecular genetic tool, their use in diagnostic DNA testing is hampered by multiple factors, particularly in familial cases. In this report we describe a protocol that can be used for DNA testing in well defined familial cases or proven de novo cases, and in the differential diagnosis of muscular dystrophy patients clinically suspected of having FSHD. In addition, we describe a prenatal diagnosis performed for FSHD1. Images

Bakker, E; Van der Wielen, M J; Voorhoeve, E; Ippel, P F; Padberg, G W; Frants, R R; Wijmenga, C

1996-01-01

452

Relatively low proportion of dystrophin gene deletions in Israeili Duchenne and Becker muscular dystrophy patients  

SciTech Connect

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the X-linked dystrophin gene. The most common mutations in western populations are deletions that are spread non-randomly throughout the gene. Molecular analysis of the dystrophin gene structure by hybridization of the full length cDNA to Southern blots and by PCR in 62 unrelated Israeli male DMD/BMD patients showed deletions in 23 (37%). This proportion is significantly lower than that found in European and North American populations (55-65%). Seventy-eight percent of the deletions were confined to exons 44-52, half of these exons 44-45, and the remaining 22% to exons 1 and 19. There was no correlation between the size of the deletion and the severity of the disease. All the deletions causing frameshift resulted in the DMD phenotypes. 43 refs., 1 fig., 1 tab.

Shomrat, R.; Gluck, E.; Legum, C.; Shiloh, Y. [Tel Aviv Univ. (Israel)

1994-02-15

453

[Staircase phenomenon in children with progressive muscular dystrophy and dermatomyositis].  

PubMed

The electrical and mechanical activity of the isometric twitch of flexor carpi ulnaris muscle during two per second indirect supramaximal stimulation for 90 sec was examined in 14 children with muscular distrophy and 8 children with dermatomyositis. The muscle electrical responses show no significant changes in the amplitude of its first negative phase. The first derivative of the dinamogram shows some of the following abnormalities in 8 of the examined children with muscular distrophy and in 2 of these with dermatomyositis: 1. Prolonged and increased negative staircase; 2. Insufficient or absent positive staircase potentiation. These abnormalities of the staircase phenomenon disclose disorders of the contractile function of the examined muscle. PMID:213914

Uzunova, M; Gatev, V; Stomatova, L

1978-01-01

454

Lack of Functional Benefit with Glutamine versus Placebo in Duchenne Muscular Dystrophy: A Randomized Crossover Trial  

Microsoft Academic Search

BackgroundOral glutamine decreases whole body protein breakdown in Duchenne muscular dystrophy (DMD). We evaluated the functional benefit of 4 months oral glutamine in DMD.Methodology\\/Principal Findings30 ambulant DMD boys were included in this double-blind, randomized crossover trial with 2 intervention periods: glutamine (0.5 g\\/kg\\/d) and placebo, 4 months each, separated by a 1-month wash-out, at 3 outpatient clinical investigation centers in

Elise Mok; Guy Letellier; Jean-Marie Cuisset; André Denjean; Frédéric Gottrand; Corinne Alberti; Régis Hankard; Katrina Gwinn

2009-01-01

455

The organisation of spinal projecting brainstem neurons in an animal model of muscular dystrophy  

Microsoft Academic Search

Previous studies we performed on the mdx mouse demonstrated marked central nervous system alterations in this model of human Duchenne muscular dystrophy, such as reduction in number and pathological changes of cortico-spinal neurons. Prompted by these findings we extended the survey of the mdx brain to the major brainstem-descending pathways: the rubro-, vestibulo-, reticulo-, and raphe-spinal projections. Horseradish peroxidase microinjections

Donatella Carretta; Marialaura Santarelli; Duccio Vanni; Riccardo Carrai; Alessandro Sbriccoli; Francesco Pinto; Diego Minciacchi

2001-01-01

456

Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is a dynamic nuclear and sarcomeric protein  

Microsoft Academic Search

Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is a candidate gene for mediating FSHD pathophysiology, however, very little is known about the endogenous FRG1 protein. This study uses immunocytochemistry (ICC) and histology to provide insight into FRG1’s role in vertebrate muscle development and address its potential involvement in FSHD pathophysiology. In cell culture, primary myoblast\\/myotube cultures, and mouse and

Meredith L. Hanel; Chia-Yun Jessica Sun; Takako I. Jones; Steven W. Long; Simona Zanotti; Derek Milner; Peter L. Jones

2011-01-01

457

Dual exon skipping in myostatin and dystrophin for Duchenne muscular dystrophy  

Microsoft Academic Search

Background  Myostatin is a potent muscle growth inhibitor that belongs to the Transforming Growth Factor-? (TGF-?) family. Mutations leading\\u000a to non functional myostatin have been associated with hypermuscularity in several organisms. By contrast, Duchenne muscular\\u000a dystrophy (DMD) is characterized by a loss of muscle fibers and impaired regeneration. In this study, we aim to knockdown\\u000a myostatin by means of exon skipping,

Dwi U Kemaladewi; Willem MH Hoogaars; Sandra H van Heiningen; Samuel Terlouw; David JJ de Gorter; Johan T den Dunnen; Gert Jan B van Ommen; Annemieke Aartsma-Rus; Peter ten Dijke; Peter AC’t Hoen

2011-01-01

458

Anaesthetic considerations in patients with muscular dystrophy undergoing spinal fusion and harrington rod insertion  

Microsoft Academic Search

Charts of nine patients with Duchenne and one with Becker’s muscular dystrophy who had undergone spinal fusion and Harrington\\u000a rod insertion for scoliosis were reviewed retrospectively. The mean age was 15 years and mean angle of scoliosis was 69 degrees.\\u000a Preoperative pulmonary function studies showed a restrictive defect with a mean vital capacity of 1.3 ± 0.69 litres, 35 ±

Brian Milne; José K. Rosales

1982-01-01

459

Systemic Treatment of Duchenne Muscular Dystrophy by Antisense Oligomer-Induced Exon Skipping  

Microsoft Academic Search

\\u000a Duchenne muscular dystrophy (DMD), caused by nonsense or frame-shift mutations in the dystrophin gene, is a progressive degenerative\\u000a disease involving all the muscles body-wide. Antisense oligomer-mediated exon skipping has recently emerged as an effective\\u000a approach for the restoration of dystrophin. A clinical trial by intramuscular delivery of antisense oligonucleotide demonstrates\\u000a efficacy in principle in DMD patients, providing optimism for its

Qi Long Lu; Bo Wu

460

Duchenne muscular dystrophy and idiopathic hyperCKemia segregating in a family  

Microsoft Academic Search

A 7-month-old boy with gross motor delay and failure to thrive presented with rhabdomyolysis following an acute asthmatic episode. During hospitalization an electrocardiographic conversion to a Wolff-Parkinson-White type 1 (WPW) pattern took place. Duchenne muscular dystrophy (DMD) was suspected based on elevated creatine kinase (CK) serum levels, muscle biopsy, and family history. The diagnosis was confirmed by molecular analysis, which

Moshe Frydman; Rachel Straussberg; Ruth Shomrat; C. Legum; Yossi Shiloh

1995-01-01

461

Racial distribution of Duchenne muscular dystrophy in the West Midlands region of Britain.  

PubMed Central

In the West Midlands region of Britain, Duchenne muscular dystrophy (DMD) is twice as common as expected in Indians, and is less common than expected in Pakistanis. Although the numbers are small, they cannot be explained by any bias of ascertainment and are considered to be real. One possible mechanism for the high frequency of DMD in Indians is the presence of repetitive elements in the wild type gene which predispose to mutations.

Roddie, A; Bundey, S

1992-01-01

462

Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy  

Microsoft Academic Search

Nitric oxide (NO) is synthesized in skeletal muscle by neuronal-type NO synthase (nNOS), which is localized to sarcolemma of fast-twitch fibers. Synthesis of NO in active muscle opposes contractile force. We show that nNOS partitions with skeletal muscle membranes owing to association of nNOS with dystrophin, the protein mutated in Duchenne muscular dystrophy (DMD). The dystrophin complex interacts with an

Jay E Brenman; Daniel S Chao; Houhui Xia; Ken Aldape; David S Bredt

1995-01-01

463

Independent Cough Flow Augmentation by Glossopharyngeal Breathing Plus Table Thrust in Muscular Dystrophy.  

PubMed

OBJECTIVE: The purpose of the present study was to compare the unassisted cough peak flow (CPF) of patients affected by muscular dystrophy with CPF augmented by various techniques, including maximal depth glossopharyngeal breathing (GPB) combined with a subsequent self-induced thoracic or abdominal thrust. DESIGN: All of the motorized wheelchair-dependent patients with muscular dystrophy who had previously mastered GPB were trained at home to increase their cough efficacy. This training involved maneuvering their wheelchair against the edge of a specially built table to autonomously produce a thoracic and/or abdominal thrust timed to the opening of the glottis for an independently assisted cough. Both unassisted and variously assisted CPFs were compared. RESULTS: The 18 patients (17 men/1 woman) with muscular dystrophy, aged 21.1 ± 5.4 yrs, achieved variously assisted CPFs that were significantly higher than the spontaneous CPF (P < 0.001), with assisted CPFs but not unassisted CPFs that significantly exceeded a reported efficacious cough threshold value of 160 liters/min (P < 0.001). Moreover, increases in the CPFs by personal assistance including air stacking by manual resuscitator and thoracoabdominal thrust (326.4 ± 79.5 liters/min) or by GPB and thoracoabdominal thrust (326.4 ± 87.5 liters/min) were not significantly different (P = 0.07) from the CPFs independently attained by GPB plus independently maneuvering a wheelchair for a table thrust (310.3 ± 74.7 liters/min). CONCLUSIONS: The independently assisted (GPB plus table thrust) CPF was comparable to the CPFs that required personal assistance for air stacking and abdominal thrusts. Therefore, for patients with muscular dystrophy, this physical medicine technique and cough-assisted techniques that require personal intervention are strongly recommended. PMID:23739278

Bianchi, Carlo; Carrara, Raniero; Khirani, Sonia; Tuccio, Maria Chiara

2013-06-01

464

The enigma of 7q36 linked autosomal dominant limb girdle muscular dystrophy  

Microsoft Academic Search

IntroductionTwo families with autosomal dominant limb girdle muscular dystrophy (LGMD) have previously been linked to a locus on chromosome 7q36 10 years ago. The locus has been termed both LGMD1D and 1E, but because of lack of additional families to narrow down the linked region of interest, this disease has remained elusive.MethodsA large Finnish family was clinically and genetically investigated.

Satu Sandell; Sanna Huovinen; Jaakko Sarparanta; Helena Luque; Olayinka Raheem; Hannu Haapasalo; Peter Hackman; Bjarne Udd

2010-01-01

465

Muscular Dystrophy: The Relative Frequency in the Different Ethnic Groups in Israel  

Microsoft Academic Search

A study of muscular dystrophy in Israel revealed a high frequency of this disease among non-Ashkenazi Jews. The proportion was 10.41 non-Ashkenazi patients (specific rates per 100,000 of population) to 2.19 Ashkenazi. Tests performed on the above rates showed that a significant statistical difference (p<0.001) exists. A high frequency of consanguinity was described among non-Ashkenazi Jews. There was no difference

Edna Kott; A. Golan; Ruth Don; B. Bornstein

1973-01-01

466

Diagnostic, predictive, and prenatal testing for facioscapulohumeral muscular dystrophy: diagnostic approach for sporadic and familial cases  

Microsoft Academic Search

Facioscapulohumeral muscular dystrophy (FSHD) is one of the common inherited neuromuscular disorders. The major gene involved, FSHD1, has been localised to chromosome 4q35. This 4q35 locus, detected by pE13-11 (D4F104S1), shows a mutation frequency of about 10% of the incidence. New mutants are characterised by de novo deletions of tens to hundreds of kilobases of DNA. Although these deletion fragments

E. Bakker; M. J. R. van der Wielen; E. Voorhoeve; P. F. Ippel; G. W. A. M. Padberg; R. R. Frants; C. Wijmenga

1996-01-01

467

914. Recombinant AAV Gene Delivery of Follistatin for Muscle Enhancement in Models of Muscular Dystrophy  

Microsoft Academic Search

Objective: To determine the efficacy of recombinant adeno-associated virus (rAAV) delivering follistatin (FS), a potent inhibitor of myostatin, to a mouse model for limb-girdle muscular dystrophy and wild-type animals.Background: LGMD2D is a debilitating muscle disease of children and young adults. There is no proven treatment to delay the disease progression. Inhibition of myostatin, a negative growth modulator for muscle, can

Liza Rizo; Chris Shilling; Amanda Haidet; Priya Umapathi Umapathi; Zarife Sahenk; Jerry R. Mendell; Brian K. Kaspar

2006-01-01

468

Evolution of Gastric Electrical Features and Gastric Emptying in Children with Duchenne and Becker Muscular Dystrophy  

Microsoft Academic Search

OBJECTIVES:Although muscular dystrophy (MD) affects primarily striated muscles, smooth muscle cells of the gastrointestinal tract may also be involved. We recorded gastric electrical activity and gastric emptying time (GET) in children with MD at initial presentation and at 3-yr follow-up in order to detect gastric motor abnormalities and study their evolution along the clinical course.METHODS:Twenty children with MD (median age: