Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A large oligomeric complex of sarcolemmal glycoproteins is associated with dystrophin, the protein absent in Duchenne muscular dystrophy (DMD). The dystrophin-glycoprotein complex spans the sarcolemma, providing a link between the subsarcolemmal cytoskeleton and the extracellular matrix. It was recently shown that one component of this complex, the 50 kDa dystrophin-associated glycoprotein (50 DAG or adhalin), is deficient in severe childhood autosomal recessive muscular dystrophy with DMD-like phenotype (SCARMD). This disease, initially described in Tunisia, was also reported in patients from other North-African and Middle-Eastern countries. It has not been known whether this disease exists in other populations or regions of the world. The present study provides immunocytochemical evidence of 50 DAG specific deficiency in muscle biopsies of European sporadic patients (three French, one Italian and one Greek) who clinically presented with a Duchenne or Becker-like muscular dystrophy. This study demonstrates that SCARMD exists in distinct European populations. Without knowing the status of the 50 kDa, such patients could be either undiagnosed or misdiagnosed as Duchenne, Becker or limb girdle muscular dystrophy. Their accurate diagnosis, which is essential for genetic counseling and eventual future therapies, is now possible by immunocytochemical analysis of the 50 DAG in the biopsied skeletal muscle.
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PMID:Deficiency of the 50 kDa dystrophin associated glycoprotein (adhalin) in severe autosomal recessive muscular dystrophies in children native from European countries. 804 5

Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive (AR) muscular dystrophy which presents a clinical course indistinguishable from the Xp21 Duchenne muscular dystrophy or DMD. Recently, Othmane et al., based on a linkage study with 13q12 markers in 3 highly inbred DLMD families from Tunisia, suggested that the gene for this myopathy lies in the pericentromeric region of chromosome 13q. It is unknown if there is genetic heterogeneity causing the DLMD phenotype. Therefore, the aim of the present report is to describe the results of linkage analysis in 4 Brazilian DLMD families with 13q12 markers (D13S115 and D13S120), which were also tested for 50DAG. It was possible to exclude the 13q gene at theta = 0.10 as responsible for the DLMD phenotype in our families using both 13q12 markers, if the lod scores of each family were added up. Interestingly, 3 families were deficient for 50 DAG while one showed a positive pattern for this glycoprotein. Therefore, these results suggest: a) the DLMD phenotype is caused by more than one recessive gene; b) a gene, not located at 13q, causes deficiency of 50 DAG as a primary or secondary defect.
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PMID:Genetic heterogeneity for Duchenne-like muscular dystrophy (DLMD) based on linkage and 50 DAG analysis. 828 Nov 58

Recently, a deficiency of merosin has been reported in patients with classical congenital muscular dystrophy (CMD), while other patients, with indistinguishable clinico-pathological features, do not present this deficiency, suggesting genetic heterogeneity. The purpose of the present investigation was to assess merosin distribution and quantity in 21 clinically well characterized Brazilian CMD patients, in order to: a) estimate the proportion of merosin-deficient cases in this group of patients; b) characterize phenotypically merosin-negative, as compared to merosin-positive patients. Merosin deficiency was found in 11 patients and all the seven who had been submitted to neuroimaging studies showed evidence of periventricular dysmyelination. A normal pattern of 43 DAG was found in all patients, which suggest that this protein is not preferentially involved in a third form of merosin-positive CMD. Results from the present study are further suggestive, but do not prove, that the association of merosin deficiency with white matter alterations represents a genetic entity with common clinical, laboratory and neuroimaging findings.
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PMID:Deficiency of merosin (laminin M or alpha 2) in congenital muscular dystrophy associated with cerebral white matter alterations. 871 43

A girl born from consanguineous Turkish parents had marked hypotonia from birth and delayed milestones. She was able to stand unaided by 3 years of age with then progressive worsening of motor abilities. She had a severe non-progressive mental deficiency. Epilepsy occurred by 6 years of age. Ophthalmological investigation was normal. A marked white matter high signal was seen on magnetic resonance imaging without cortical dysplasia. Dystrophic changes were seen on muscle biopsy. Two brothers had had a similar history with early death. Muscular immunocytochemical studies showed a normal staining for dystrophin and all dystrophin related glycoproteins (including 43 and 50 DAG). Merosin staining was normal. This case differs from Fukuyama's congenital dystrophy, from merosin negative congenital muscular dystrophy, or from other congenital muscular dystrophy with CNS dysfunction. It underlines the heterogeneity of congenital muscular dystrophy and the non-specific aspect of white matter changes on neuro-imaging.
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PMID:Merosin positive congenital muscular dystrophy with mental deficiency, epilepsy and MRI changes in the cerebral white matter. 918 83

We generated a novel monoclonal antibody, DAG-6F4, against alpha-dystroglycan which immunolabels the sarcolemma in human muscle biopsies. Its seven amino-acid epitope, PNQRPEL, was identified using phage-displayed peptides and is located immediately after the highly-glycosylated mucin domain of alpha-dystroglycan. On Western blots of recombinant alpha-dystroglycan, epitope accessibility was reduced, but not entirely prevented, by glycosylation. DAG-6F4 immunolabelling was markedly reduced in muscle biopsies from Duchenne muscular dystrophy patients consistent with disruption of the dystroglycan complex. In a range of dystroglycanopathy patients with reduced/altered glycosylation, staining by DAG-6F4 was often less reduced than staining by IIH6 (antibody against the glycan epitope added by LARGE and commonly used to identify glycosylated alpha-dystroglycan). Whereas IIH6 was reduced in all patients, DAG-6F4 was hardly changed in a LARGE patient, less reduced than IIH6 in limb-girdle muscular dystrophy type 2I, but as reduced as IIH6 in some congenital muscular dystrophy patients. Although absence of the LARGE-dependent laminin-binding site appears not to affect alpha-dystroglycan stability at the sarcolemma, the results suggest that further reduction in aDG glycosylation may reduce its stability. These studies suggest that DAG-6F4 may be a useful addition to the antibody repertoire for evaluating the dystroglycan complex in neuromuscular disorders.
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PMID:A new monoclonal antibody DAG-6F4 against human alpha-dystroglycan reveals reduced core protein in some, but not all, dystroglycanopathy patients. 2538 94