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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the clinical features and the muscle pathology in 2 patients with congenital muscular dystrophy (CMD) secondary to merosin deficiency and in 2 patients with sarcoglycan (adhalin) deficiency. Electron microscopic examination revealed sarcolemmal defects in non-necrotic muscle fibers in all cases. These pathological findings are indistinguishable from those of Duchenne/Becker muscular dystrophy. We suggest that the similarities in histological findings reflect a common pathogenetic mechanism, i.e., a structural weakening of the sarcolemma with an increased susceptibility to rupture under mechanical stress. We propose the term sarcolemmopathy as an all-encompassing rubric for these disorders.
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PMID:Muscle pathology and clinical features of the sarcolemmopathies. 904 10

Two siblings with a congenital muscular dystrophy and severe mental retardation which was not due to dystrophin, merosin, or adhalin deficiency are described. These cases overlap with congenital muscular dystrophy of the Fukuyama-type but are less severe. Atypical features include limited facial involvement, retained ambulation, and severe retrocollis.
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PMID:Congenital muscular dystrophy with severe retrocollis and mental retardation: a report of two siblings. 906 86

Malignant limb-girdle muscular dystrophy (MLGMD) was proposed by Miyoshi et al. in 1966 as a clinical and genetic entity of muscular dystrophy, with clinical features similar to Duchenne muscular dystrophy but showing autosomal recessive inheritance. Recently, deficiency of alpha-sarcoglycan (adhalin), which is one of the components of dystrophin-glycoprotein complex, in the skeletal muscle has been found in several patients with MLGMD or severe childhood autosomal recessive muscular dystrophy. To investigate alpha-sarcoglycan gene mutations in patients with MLGMD, we analyzed cDNA prepared from skeletal muscle by reverse transcription polymerase chain reaction (RT-PCR), or genomic DNA prepared from peripheral blood leukocytes by PCR, using single-strand conformation polymorphism (SSCP). When products amplified by RT-PCR or PCR showed aberrant conformers on SSCP analysis, these products were sequenced by the fluorescence-based dideoxy termination method. We found missense mutations, insertions or deletions in the alpha-sarcoglycan gene in 6 families with MLGMD. In the literature, alpha-sarcoglycan gene mutations have been identified in 21 families with MLGMD/SCARMD including our 6 families. Half of the families have the cytosine to thymidine substitution at nt.229, resulting in the replacement of Arg by Cys at codon 77, and most of the mutations have been found in the region coding extracellular domain of alpha-sarcoglycan. Analysis of the alpha-sarcoglycan gene is indispensable for diagnosis, assessment of prognosis, genetic counseling, and future gene therapy in patients with autosomal recessive childhood-onset muscular dystrophy.
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PMID:[Gene analysis in patients with muscular dystrophy: alpha-sarcoglycan (adhalin) gene mutations in patients with malignant limb-girdle muscular dystrophy]. 912 Sep 97

The group of autosomal recessive (AR) muscular dystrophies includes, among others, two main clinical entities, the limb-girdle muscular dystrophies (LGMDs) and the distal muscular dystrophies. The former are characterized mainly by muscle wasting of the upper and lower limbs, with a wide range of clinical severity. This clinical heterogeneity has been demonstrated at the molecular level, since the genes for six AR forms have been cloned and/or have been mapped to 15q15.1 (LGMD2A), 2p12-16 (LGMD2B), 13q12 (LGMD2C), 17q12-q21.33 (LGMD2D),4q12 (LGMD2E), and 5q33-34 (LGMD2F). The AR distal muscular dystrophies originally included two subgroups, Miyoshi myopathy, characterized mainly by extremely elevated serum creatine kinase (CK) activity and by a dystrophic muscle pattern, and Nonaka myopathy, which is distinct from the others because of the normal to slightly elevated serum CK levels and a myopathic muscle pattern with rimmed vacuoles. With regard to our unclassified AR LGMD families, analysis of the affected sibs from one of them (family LG61) revealed some clinical and laboratory findings (early involvement of the distal muscles, mildly elevated serum CK levels, and rimmed vacuoles in muscle biopsies) that usually are not observed in the analysis of patients with LGMD2A-LGMD2F. In the present investigation, through a genomewide search in family LG61, we demonstrated linkage of the allele causing this form of muscular dystrophy to a 3-cM region on 17q11-12. We suggest that this form, which, interestingly, clinically resembles AR Kugelberg-Welander disease, should be classified as LGMD2G. In addition, our results indicate the existence of still another locus causing severe LGMD.
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PMID:The seventh form of autosomal recessive limb-girdle muscular dystrophy is mapped to 17q11-12. 924 96

Recent advances in molecular genetics research have revolutionised our understanding of the childhood muscular dystrophies. The first breakthrough came in 1987 with the identification of the gene for dystrophin, the protein that is abnormal in X-linked Duchenne muscular dystrophy. Dystrophin is bound to a complex of proteins in the muscle membrane, and primary abnormalities of these proteins have now been identified as the cause of some autosomally inherited forms of muscular dystrophy. A group of transmembrane proteins known as alpha- (adhalin) beta-, gamma- and delta-sarcoglycan are deficient in autosomal recessive limb-girdle muscular dystrophy, and the extracellular matrix protein merosin (alpha2-laminin), is deficient in a subset of patients with congenital muscular dystrophy. Identification of primary deficiencies in these 'dystrophin associated proteins' will result in improved diagnostic accuracy, more accurate genetic counselling and, in some cases, the availability of prenatal diagnosis.
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PMID:Recent advances in diagnosis of the childhood muscular dystrophies. 925 92

Immunocytochemical deficiency of alpha-sarcoglycan (adhalin) in the skeletal muscle that is associated with normal dystrophin expression has been called adhalinopathy. However, recent molecular biological and genetic studies revealed that alpha-sarcoglycan is one of four subunits of sarcoglycans (alpha-delta) or sarcoglycan complex. Mutations of any one of the genes of these subunits cause loss of sarcoglycan complex, and therefore they are now called sarcoglycanopathy or limb-girdle muscular dystrophy (LGMD) 2C-2F. The frequency of sarcoglycanopathy is about 5-10% of dystrophin-normal muscular dystrophy. Mutation of alpha-sarcoglycan gene is most frequent (34%) among the four sarcoglycan genes as shown in the tables. However, 38% of the patients with sarcoglycanopathy have no mutation, implying the presence of yet unknown sarcoglycan(s) and/or interacting protein(s) with sarcoglycan complex.
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PMID:[The frequency of patients with adhalin deficiency in a muscular dystrophy patient population]. 943 29

A new homozygous alpha-sarcoglycan (adhalin) gene mutation was found in a Japanese patient with severe childhood autosomal recessive muscular dystrophy (SCARMD). Muscle biopsy specimens from the patient showed marked reduction but not complete deficiency of alpha-sarcoglycan. The sequence of part of exon 3 of the alpha-sarcoglycan gene exhibited a cytosine to thymidine substitution at nucleotide position 220. Since the same mutation was not found in 100 normal control samples, this new alpha-sarcoglycan gene mutation is not a polymorphism but is presumed to be responsible for the marked reduction of alpha-sarcoglycan in skeletal muscle. Most patients with homozygous alpha-sarcoglycan gene mutation were reported to show complete alpha-sarcoglycan deficiency. Present case showed the homozygous missense mutation of alpha-sarcoglycan and associated with incomplete alpha-sarcoglycan deficiency and severe clinical phenotype.
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PMID:New missense mutation in the alpha-sarcoglycan gene in a Japanese patient with severe childhood autosomal recessive muscular dystrophy with incomplete alpha-sarcoglycan deficiency. 945 86

Muscle biopsies of 13 congenital muscular dystrophy (CMD) patients were investigated for the expression of laminin-alpha2 (merosin), beta-dystroglycan, alpha-sarcoglycan (adhalin) and dystrophin. Expression of these proteins was normal in six out of eight patients with pure-CMD, in three non-Japanese patients clinically resembling Fukuyama-CMD (F-CMD), and in two patients with Walker-Warburg syndrome (WWS). The two 'pure'-CMD patients with white matter hypodensity showed severely decreased laminin-alpha2 expression and normal expression of the other proteins. Our findings in the non-Japanese patients, clinically resembling F-CMD, are different from those in Japanese cases with F-CMD in the literature. Consequently, our patients suffer from WWS or from another yet undetermined form of CMD.
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PMID:Laminin-alpha2 (merosin), beta-dystroglycan, alpha-sarcoglycan (adhalin), and dystrophin expression in congenital muscular dystrophies: an immunohistochemical study. 963 97

Linkage studies have confirmed the existence of clinical an genetic heterogeneity among the muscular dystrophies due to adhalin deficiency. We present the clinical, histological and genetic characteristics in a case of primary adhalinopathy (deficiency of the 50 kD subunit or alpha-sarcoglycan). It was a 19 years-old woman, born of non consanguineous parents, who shows a long evolution myopathy with onset before age 7, a severe evolution and becoming wheelchair bound at 10 years. She showed evident calf pseudohypertrophy and serum creatinkinase (CK) levels were elevated (40-180 times the standard level). The histological pattern showed a destructed fascicular architecture in agreement with severe muscular dystrophy, normal staining with anti-dystrophin monoclonal antibodies and abnormal staining pattern with anti-adhalin antibodies. The molecular study evidenced an homozygous point mutation (Arg-->Cys) at position 77 of exon 3 of the gene coding for the 50 kD subunit of the alpha-sarcoglycan complex localised in chromosome 17. In the light of this case, we suggest a revision of the diagnostic orientation in the muscular dystrophies and we review the new taxonomy of the limb-girdle muscular dystrophies, remarking the clinical signs which could indicate a given genetic locus.
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PMID:[Muscular dystrophy due to a mutation in the gene of alpha-sarcoglycan subunit of dystrophin associated protein complex]. 964 69

Abnormalities of dystrophin are a common cause of muscular dystrophy and testing for dystrophin gene or protein has become a part of routine diagnostic evaluation of patients who present with progressive proximal muscle weakness, high serum creatine kinase concentrations, and histopathological evidence of a dystrophic process. Patients who have no dystrophin abnormalities are assumed to have autosomal recessive muscular dystrophy. In a family consisting of 5 sibs, 2 mentally normal brothers presented with abnormal gait and protrusion of chest and hips. Muscle biopsy from one of them showed dystrophic changes and reduced patchy binding of dystrophin. No detectable deletion was observed in the patient's DNA and his brother with cDMD probes. Dystrophin associated proteins, beta-dystroglycan showed discontinuous immunostaining in the sarcolemma and alpha-sarcoglycan (adhalin) was totally absent, while beta-, gamma-, and delta-sarcoglycans were highly reduced. Immunoblot analysis showed dystrophin of normal molecular weight but of decreased quantity, beta-dystroglycan was reduced by about 37% while alpha-sarcoglycan was completely absent. This study is a first attempt for a systematic clinical, genetic and molecular investigation of the autosomal recessive LGMD in India.
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PMID:Deficiency of the 50 kDa dystrophin-associated-glycoprotein (adhalin) in an Indian autosomal recessive limb girdle muscular dystrophy patient : immunochemical analysis and clinical aspects. 1130 36


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