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

Severe autosomal recessive muscular dystrophy (SCARMD), McKusick n. 253700, has been originally described in North-African populations, in which significant linkage has been established with DNA markers mapping to the proximal region of the long arm of chromosome 13, without evidence for heterogeneity of the SCARMD locus in these populations. A striking feature of this disease is the isolated deficiency of adhalin, a sarcolemmal 50 kDa dystrophin-associated glycoprotein. We report a non-inbred French family with a milder progressive form of muscular dystrophy affecting subjects of both sexes. The parents are not affected suggesting an autosomal recessive transmission. In 4 siblings displaying mild to overt clinical signs of muscular dystrophy, serum creatine kinase was high, and muscle specimens showed variable degree of necrosis-regeneration with little fibrosis. In the 4 cases adhalin was completely absent in muscle sections, whereas dystrophin and the other members of the dystrophin-associated protein complex were normal, except for the 35 kDa dystrophin-associated glycoprotein which was decreased as usually observed in SCARMD. Linkage and homogeneity analysis using 4 microsatellite markers of chromosome 13q that are linked to the North-African SCARMD locus were performed in this family. Results show that the morbid locus involved in this family does not map to the same region as the SCARMD locus. This second locus may be involved in sporadic cases of muscular dystrophy with adhalin deficiency that have been reported in Europe.
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PMID:Genetic heterogeneity of severe childhood autosomal recessive muscular dystrophy with adhalin (50 kDa dystrophin-associated glycoprotein) deficiency. 798 94

Dystrophin is associated with several novel sarcolemmal proteins, including a laminin-binding extracellular glycoprotein of 156 kD (alpha-dystroglycan) and a transmembrane glycoprotein of 50 kD (adhalin). Deficiency of adhalin characterizes a severe autosomal recessive muscular dystrophy prevalent in Arabs. Here we report for the first time two mongoloid (Japanese) patients with autosomal recessive muscular dystrophy deficient in adhalin. Interestingly, adhalin was not completely absent and was faintly detectable in a patchy distribution along the sarcolemma in our patients. Although the M and B2 subunits of laminin were preserved, the B1 subunit was greatly reduced in the basal lamina surrounding muscle fibers. Our results raise a possibility that the deficiency of adhalin may be associated with the disturbance of sarcolemma-extracellular matrix interaction leading to sarcolemmal instability.
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PMID:Abnormal expression of laminin suggests disturbance of sarcolemma-extracellular matrix interaction in Japanese patients with autosomal recessive muscular dystrophy deficient in adhalin. 804 Mar 15

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

Adhalin, the 50 kDa dystrophin-associated glycoprotein, is deficient in skeletal muscle of patients having severe childhood autosomal recessive muscular dystrophy (SCARMD). In several North African families, SCARMD has been linked to chromosome 13q, but SCARMD has been excluded from linkage to this locus in other families. We have now cloned human adhalin cDNA and mapped the adhalin gene to chromosome 17q12-q21.33, excluding it from involvement in 13q-linked SCARMD. However, one allelic variant of a polymorphic microsatellite located within intron 6 of the adhalin gene cosegregated perfectly with the disease phenotype in a large family. Furthermore, missense mutations were identified within the adhalin gene that might cause SCARMD in this family. Thus, the adhalin gene is involved in at least one form of autosomal recessive muscular dystrophy.
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PMID:Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy. 806 11

To determine if dystrophin and dystrophin-associated glycoproteins (DAGs) are involved in muscle fiber necrosis in the dystrophic hamster, we examined NSJ-my/my (homozygous dystrophic) hamsters introduced from the BIO14.6 strain, by immunohistochemical and immunoblotting methods. Antibodies against dystrophin, utrophin and DAGs including 50DAG (A2), 43DAG (A3a) and 35DAG (A4) were employed for the examination. Dystrophin was stained strongly and utrophin stained very faintly along the sarcolemma of the dystrophic hamster, similar to the control. On the other hand, in the dystrophic hamster 50DAG (A2) and 35DAG (A4) were selectively defective, and 43DAG (A3a) was also decreased, although to a lesser degree. Since these results were almost identical to those seen in severe childhood autosomal recessive muscular dystrophy (SCARMD), the dystrophic hamster appears to be an animal model of SCARMD in which defects in DAGs may result in muscle fiber necrosis despite normal dystrophin expression.
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PMID:Selective defect in dystrophin-associated glycoproteins 50DAG (A2) and 35DAG (A4) in the dystrophic hamster: an animal model for severe childhood autosomal recessive muscular dystrophy (SCARMD). 817 51

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

Autosomal recessive limb-girdle muscular dystrophies (AR LGMD) represent a heterogeneous group of diseases with a wide spectrum of clinical variability, classified phenotypically into two main groups, the most severe forms (Duchenne-like muscular dystrophy, DLMD, or severe childhood autosomal recessive muscular dystrophy, SCARMD) and the milder forms. Four genes causing AR LGMD have been mapped: the 15q (LGMD2a), the 2p (LGMD2b), the 13q locus (LGMD2c) and the adhalin gene on chromosome 17q (LGMD2d). In the present report we have performed linkage analysis with 17q markers in three mild AR LGMD and in four DLMD families with adhalin deficiency and unlinked to 2p, 15q or 13q genes. Linkage was observed only among the mild cases. Patients from these three 17q-linked families showed near or total deficiency of adhalin in muscle biopsies. An identical missense mutation was identified in all three 17q-linked unrelated families. These results indicate that AR LGMD with a mild phenotype is caused by mutations in the adhalin gene. In addition, they demonstrate that there is at least one other locus for DLMD associated with adhalin deficiency.
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PMID:A common missense mutation in the adhalin gene in three unrelated Brazilian families with a relatively mild form of autosomal recessive limb-girdle muscular dystrophy. 852 3

Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of dystrophies in which weakness and wasting initially appear at proximal groups of pelvic and shoulder girdles. Families in which LGMD is inherited as an autosomal recessive and rarely autosomal dominant trait were separated. Among autosomal recessive families, cases with rapid progression, called severe childhood autosomal recessive muscular dystrophy (SCARMD) were isolated. In some of these families linkage to chromosome 13 has been demonstrated. In other families especially those with relatively slower progression the genes were localised on chromosomes 2, 15. In families with adhalin mutations variability of clinical presentation is observed. In one of the described families with autosomal dominant inheritance the linkage to chromosome 5 has been established. Clinical and genetic studies of a large cohort of patients with limb-girdle muscular dystrophies enables the creation of new LGMD diagnostic criteria which facilitates proper genetic counselling.
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PMID:[Clinical and genetic heterogeneity of limb-girdle muscular dystrophy]. 854 36

We recently reported the selective reduction of the B1 subunit of laminin in two Japanese patients with adhalin deficiency. We here investigated immunohistochemically the expression of other components of the extracellular matrix (ECM), including collagen type IV, heparan sulfate proteoglycan can (HSPG), chondroitin-4-sulfate proteoglycan, decorin, and fibronectin in adhalin deficiency, compared with other types of muscular dystrophy. We found a reduction of HSPG on the basal lamina surrounding each muscle fiber in adhalin deficiency compared with HSPG in other diseases. This finding may be characteristic evidence of the disturbance of the sarcolemma-ECM interaction and the sarcolemmal instability in adhalin deficiency. Recently, a direct role of HSPG in fibroblast growth factor (FGF) signal transduction was demonstrated. Further investigation is required to determine if the dysfunction of FGF is relevant to the pathogenesis of adhalin deficiency.
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PMID:Abnormal expression of heparin sulfate proteoglycan on basal lamina of muscle fibers in two Japanese patients with adhalin deficiency. 858 Jul 28

The clinical, biochemical and histochemical features of 14 patients (nine females and five males) with severe childhood autosomal recessive muscular dystrophy (SCARMD) seen at a tertiary hospital in Riyadh from 1982 to 1993 are described. Onset was at 3 to 9 (median 3) years and four of five children aged > 12 years lost ambulation. Five of the eight pairs of parents were closely consanguineous. The mean creatine kinase was 20 times the upper normal limit. Histochemistry of muscle showed dystrophic features in all cases, and dystrophin was positive in all cases examined (N = 6). Three patients (two girls and a boy) were deficient in adhalin, the 50-kDa dystorphin-associated glycoprotein. A boy aged 13 years had rapidly progressing disease. Another boy of the same age (from a family characterized by early onset and slower progression) had normal dystrophin and adhalin. The clinical features conformed with previous observations from Sudan, North Africa and Qatar in the Arabian Peninsula. The disease is common in Saudi Arabia and seems to be more prevalent than Duchenne muscular dystrophy.
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PMID:Clinical and molecular pathological features of severe childhood autosomal recessive muscular dystrophy in Saudi Arabia. 863 23


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