A novel de novo mutation in the triple helix of the COL6A3 gene in a two-generation Italian family affected by Bethlem myopathy. A diagnostic approach in the mutations' screening of type VI collagen

Neuromuscul Disord. 1999 Jun;9(4):264-71. doi: 10.1016/s0960-8966(99)00014-0.


Bethlem myopathy is an autosomal dominant inherited disease producing a mild neuromuscular disorder, characterized mainly by muscular weakness and multiple joint contractures. Bethlem myopathy is caused by mutations in one of the three chains of collagen type VI. Here we report the clinical description and the molecular characterization of the defect in a two-generation Italian family in which a Gly-->Arg substitution disrupts the triple helix structure of the alpha 3 chain of collagen type VI, an ubiquitous glycoprotein of the extracellular matrix. In this family the identification of the mutation also allowed one to exclude the disease in the grandfather. It is noteworthy that the father of the proband carries a de novo mutation, the first described for Bethlem myopathy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amino Acid Substitution / genetics
  • Cells, Cultured
  • Child
  • Collagen / genetics*
  • DNA / chemistry
  • DNA / genetics*
  • DNA Mutational Analysis
  • Female
  • Fibroblasts
  • Heteroduplex Analysis
  • Humans
  • Male
  • Muscle, Skeletal / pathology
  • Mutation / genetics*
  • Neuromuscular Diseases / diagnosis*
  • Neuromuscular Diseases / genetics*
  • Neuromuscular Diseases / pathology
  • Pedigree
  • Polymorphism, Genetic
  • RNA / genetics
  • RNA / isolation & purification
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Skin / pathology


  • RNA
  • Collagen
  • DNA