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Genotype-phenotype correlations in 35 Brazilian families with sarcoglycanopathies including the description of three novel mutations
  1. E S Moreira,
  2. M Vainzof,
  3. O T Suzuki,
  4. R C M Pavanello,
  5. M Zatz,
  6. M R Passos-Bueno
  1. Departamento de Biologia e Centro de Estudos do Genoma Humano, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil
  1. Correspondence to:
 Dr M R Passos-Bueno, Departamento de Biologia, Instituto de Biociências, Rua do Matão 277, Sala 200, CEP 05508-900, São Paulo, SP, Brasil;

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The limb-girdle muscular dystrophies (LGMDs) are genetically determined progressive disorders clinically defined by the primary involvement of the pelvic and shoulder girdle musculature.1 Among autosomal recessive LGMDs (LGMD 2), sarcoglycanopathies (LGMD 2C-2F) represent a subgroup caused by mutations in one of the genes that encode γ-, α-, β-, and δ-sarcoglycans (SGs), respectively.2–6 The SGs are transmembrane glycoproteins which, together with sarcospan, dystrophin, dystroglycans, syntrophins, and α-dystrobrevin, constitute the dystrophin-glycoprotein complex (DGC).7–10 In addition to the four SGs that comprise the SG-sarcospan subcomplex of the DGC in striated muscle,11 a fifth SG, named ε-SG, is expressed in a wide variety of tissues.12,13 In smooth muscle, ε-SG replaces α-SG as an integral component of a unique SG-sarcospan complex composed of ε-, β-, γ- and δ-SGs and sarcospan.14 Interestingly, it has been shown that mutations in ε-SG cause myoclonus-dystonia syndrome, an autosomal dominant non-degenerative central nervous system disorder.15

It is well recognised that the DGC acts as a linker between the cytoskeleton of the muscle cell and the extracellular matrix, providing mechanical support to the plasma membrane during myofibre contraction.9,16,17 Besides this structural function, there is now increasing evidence that the DGC might play a role in cellular communication, as highlighted by its interaction with signalling molecules such as calmodulin, nitric oxide synthase, and Grb2.10,17 So far, 41, 20, 10, and six distinct pathogenic mutations have been found in the α- (LGMD 2D), β- (LGMD 2E), γ- (LGMD 2C), and δ-SG (LGMD 2F) genes, respectively (Leiden Muscular Dystrophy pages, Severe clinical Duchenne-like presentations tend to be more common among these patients, with onset occurring early in childhood and confinement to a wheelchair before the age of 1618–23; however, milder courses have also been described …

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