Missense mutation in a von Willebrand factor type A domain of the α3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

Te Cheng Pan, Rui Zhu Zhang, Margaret A. Pericak-Vance, Rup Tandan, Timothy Fries, Jeffrey M. Stajich, Kristi Viles, Jeffery M. Vance, Mon Li Chu, Marcy C. Speer

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G→A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.

Original languageEnglish (US)
Pages (from-to)807-812
Number of pages6
JournalHuman molecular genetics
Issue number5
StatePublished - May 1998
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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