Toggle Main Menu Toggle Search

Open Access padlockePrints

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

Lookup NU author(s): Professor Volker StraubORCiD


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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.

Publication metadata

Author(s): Straub V; Herrmann R; Blank M; Kutzick C; Franke N; Jacob EN; Lenard HG; Kroger S; Voit T

Publication type: Article

Publication status: Published

Journal: Human Molecular Genetics

Year: 2000

Volume: 9

Issue: 15

Pages: 2335-2340

ISSN (print): 0964-6906

ISSN (electronic): 1460-2083

Publisher: Oxford University Press