Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E

Claudio Semplicini, John Vissing, Julia R Dahlqvist, Tanya Stojkovic, Luca Bello, Nanna Witting, Morten Duno, France Leturcq, Cinzia Bertolin, Paola D'Ambrosio, Bruno Eymard, Corrado Angelini, Luisa Politano, Pascal Laforêt, Elena Pegoraro

50 Citations (Scopus)

Abstract

OBJECTIVE: To determine the clinical spectrum of limb-girdle muscular dystrophy 2E (LGMD2E) and to investigate whether genetic or biochemical features can predict the phenotype of the disease.

METHODS: All LGMD2E patients followed in participating centers were included. A specific clinical protocol was created, including quantitative evaluation of motor, respiratory, and cardiac function. Phenotype was defined as severe or mild if the age at loss of ambulation occurred before or after 18 years. Molecular analysis of SGCB gene and biochemical features of muscle biopsies were reviewed.

RESULTS: Thirty-two patients were included (16 male, 16 female; age 7-67 years; 15 severe, 12 mild, and 5 unknown). Neurologic examination showed proximal muscle weakness in all patients, but distal involvement was also observed in patients with severe disease early in the disease course. Cardiac involvement was observed in 20 patients (63%) even before overt muscle involvement. Six patients had restrictive respiratory insufficiency requiring assisted ventilation (19%). Seventeen different mutations were identified, and 3 were recurrent. The c.377_384dup (13 alleles) was associated with the severe form, the c.-22_10dup (10) with the milder form, and the c.341C>T (9) with both. The entire sarcoglycan complex was undetectable by muscle immunohistochemistry or Western blot in 9/10 severe cases and reduced in 7/7 mild cases. The residual amount of sarcoglycan in muscle resulted a predictor of age at loss of ambulation.

CONCLUSIONS: This study expands the spectrum of phenotype in β-sarcoglycanopathy and provides strong evidence that severity of clinical involvement may be predicted by SGCB gene mutation and sarcoglycan protein expression.

Original languageEnglish
JournalNeurology
Volume84
Issue number17
Pages (from-to)1772-81
Number of pages10
ISSN0028-3878
DOIs
Publication statusPublished - 28 Apr 2015

Keywords

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Child
  • Consanguinity
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Phenotype
  • Prognosis
  • Sarcoglycanopathies
  • Sarcoglycans
  • Severity of Illness Index
  • Young Adult

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