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Online mutation report
Novel sarcoglycan gene mutations in a large cohort of Italian patients
  1. C Boito1,
  2. M Fanin1,
  3. G Siciliano2,
  4. C Angelini1,
  5. E Pegoraro1
  1. 1Department of Neurological and Psychiatric Sciences, University of Padova, Italy
  2. 2Department of Neurosciences, University of Pisa, Italy
  1. Correspondence to:
 Dr E Pegoraro, Department of Neurological and Psychiatric Sciences, University of Padova, Via Giustiniani 5, 35128 Padova, Italy; 
 elena.pegoraro{at}unipd.it.

https://doi.org/10.1136/jmg.40.5.e67

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    The sarcoglycanopathies are a group of autosomal recessive limb girdle muscular dystrophies (LGMD) resulting from mutations in the genes encoding sarcoglycans (SG), small glycoproteins localised to the plasma membrane of muscle fibres. The sarcoglycans consist of a single transmembrane domain, a small intracellular domain, and a large extracellular domain, and their molecular weight ranges from 35 to 50 kDa. The sarcoglycan complex, which is composed of α-SG, β-SG, γ-SG, and δ-SG, is part of the dystrophin associated glycoprotein (DAG) complex, and it acts as a link between the extracellular matrix and the cytoskeleton, confers structural stability to the sarcolemma, and protects muscle fibres from mechanical stress during muscle contraction.1–3

    The diseases associated with SG gene mutations (α-SG (SGCA), LGMD2D, MIM 600119; β-SG (SGCB), LGMD2E, MIM 604286; γ-SG (SGSG), LGMD2C, MIM 253700; δ-SG (SGCD), LGMD2F, MIM 601287) are rare disorders in the general population, but represent a sizeable proportion of all muscular dystrophies with normal dystrophin (about 10–20% of cases).4–8 LGM2D is the most frequent sarcoglycanopathy,9 followed by LGMD2C10 and LGMD2E,11,12 while the most rare is LGMD2F.13

    Since the first description of SG gene mutation in LGMD2D,9,14 a large number of patients and mutations have been described,10–13,15–28 and correlations of genotype with clinical phenotype and protein expression have been investigated.29,30 Null mutations in any of the SG genes usually result in a severe phenotype (sometimes resembling Duchenne-like muscular dystrophy) and at the muscle biopsy level absence of the corresponding protein, whereas missense mutations have variable effects on both phenotype and protein level.

    Studies of muscle biopsies from patients with null mutations in the SG genes showed that the absence of one SG subunit has consequences for the stability of the entire complex depending on …

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