| Abstract | 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 pathogenesis 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 caveolin-3 deficiency in her dystrophic skeletal muscle as a result of a heterozygous 136G-->A substitution in the caveolin-3 gene. The novel sporadic missense mutation in the caveolin signature sequence of the caveolin-3 gene changes an alanine to a threonine (A46T) and prevents the localization of caveolin-3 to the plasma membrane in a dominant negative fashion. Caveolin-3 has been suggested to interact with the dystrophin-glycoprotein complex, which in striated muscle fibers links the cytoskeleton to the extracellular matrix and with neuronal nitric oxide synthase. Similar to dystrophin-deficient Duchenne muscular dystrophy, a secondary decrease in neuronal nitric oxide synthase and alpha-dystroglycan expression was detected in the caveolin-3-deficient patient. These results implicate an important function of the caveolin signature sequence and common mechanisms in the pathogenesis of dystrophin-glycoprotein complex-associated muscular dystrophies with caveolin-3-deficient limb girdle muscular dystrophy. |
| Authors | R Herrmann, V Straub, M Blank, C Kutzick, N Franke, E N Jacob, H G Lenard, S Kröger, T Voit
(Affiliation: Department of Pediatrics and Pediatric Neurology, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany.)
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| Journal | Human molecular genetics
(Hum Mol Genet)
Vol. 9
Issue 15
Pg. 2335-40
(Sep 22 2000)
ISSN: 0964-6906 ENGLAND |
| PMID | 11001938
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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| Chemical References |
- Cav3 protein, mouse
- Caveolin 3
- Caveolins
- Cytoskeletal Proteins
- DAG1 protein, human
- Membrane Glycoproteins
- Muscle Proteins
- Dystroglycans
- Nitric Oxide Synthase
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| Topics |
- Amino Acid Substitution
- Animals
- Blotting, Western
- Caveolin 3
- Caveolins
(analysis, genetics, metabolism)
- Child, Preschool
- Cytoskeletal Proteins
(metabolism)
- DNA Mutational Analysis
- Dystroglycans
- Female
- Humans
- Immunohistochemistry
- Membrane Glycoproteins
(metabolism)
- Mice
- Muscle Proteins
(analysis, genetics, metabolism)
- Muscular Dystrophies
(genetics, metabolism, pathology)
- Mutation, Missense
- Nitric Oxide Synthase
(metabolism)
- Pedigree
- Polymerase Chain Reaction
- Polymorphism, Single-Stranded Conformational
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