A heterozygous splice site mutation in COL6A1 leading to an in-frame deletion of the α1(VI) collagen chain in an Italian family affected by Bethlem myopathy

Guglielmina Pepe, Betti Giusti, Enrico Bertini, Tamara Brunelli, Biagio Saitta, Paolo Comeglio, Angela Bolognese, Luciano Merlini, Giorgio Federici, Rosanna Abbate, Mon Li Chu

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Bethlem myopathy is a mild neuromuscular disorder with proximal muscular weakness and early flexion contractures. It is an autosomal dominant disease due to mutations in type VI collagen genes. We found a T→C substitution at the +2 position of COL6A1 intron 14 in a family, leading to skipping of exon 14 and an in-frame deletion of 18 amino acids in the triple-helical domain of the α1(VI) collagen chain. The deletion included a cysteine residue believed to be involved in the assembly of type VI collagen dimers intracellularly, prior to the protein secretion. Analysis of the affected fibroblasts showed that the shortened α1(VI) collagen chains were synthesized but not secreted by the cells and that the amount of type VI collagen microfibrils deposited by the cells was reduced. The results suggest that the clinical phenotype is due to a reduction in the level of type VI collagen in the extracellular matrix.

Original languageEnglish
Pages (from-to)802-807
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - May 19 1999



  • Bethlem myopathy
  • COL6A1 gene
  • Collagen type VI
  • Neuromuscular disease

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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