Novel COL6A1 splicing mutation in a family affected by mild Bethlem myopathy

Olga Camacho Vanegas, Rui Zhu Zhang, Patrizia Sabatelli, Giovanna Lattanzi, Paola Bencivenga, Betti Giusti, Marta Columbaro, Mon Li Chu, Luciano Merlini, Guglielmina Pepe

Research output: Contribution to journalArticlepeer-review


Bethlem myopathy is an early-onset benign myopathy characterized by proximal muscular weakness and multiple flexion contractures. It is a dominantly inherited disorder associated with mutations in the three COL6 genes encoding type VI collagen. We detected a g→a substitution at +1 position of COL6A1 intron 3 in a four-generation Italian family affected by a mild form of Bethlem myopathy. The mutation results in the activation of a cryptic splice donor site at the 3′ end of exon 3, leading to the loss of 66 nucleotides and an "in-frame" deletion of 22 amino acids in the NH2-domain. Molecular analysis on fibroblasts of the propositus showed that the mutated mRNA was present and stable, but the mutated protein could not be detected. Western blot and immunofluorescence analyses showed a decreased level of collagen VI synthesis and deposition in fibroblasts of the propositus. Together, the results suggest that the mutated protein was highly unstable and rapidly degraded, and that the mild phenotype was caused by a reduced amount of normal collagen VI microfibrils. In addition, we demonstrated that lymphocytes can be used for the first mutation screening analysis of patients with Bethlem myopathy.

Original languageEnglish
Pages (from-to)513-519
Number of pages7
JournalMuscle and Nerve
Issue number4
Publication statusPublished - 2002


  • Bethlem myopathy
  • COL6A1
  • Collagen type VI
  • Neuromuscular disorder
  • Splicing mutation

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)


Dive into the research topics of 'Novel COL6A1 splicing mutation in a family affected by mild Bethlem myopathy'. Together they form a unique fingerprint.

Cite this