ClinVar

In a 32-year-old man with Bethlem myopathy (BTHLM1A; 158810), Lamande et al. (1999) identified a heterozygous G-to-A transition at the +1 position of intron 14 of the COL6A1 gene, which resulted in skipping of exon 14 and deletion of 18 amino acids from the triple-helical domain of the COL6A1 chain. The mutant COL6A1 chains associated intracellularly with COL6A2 (120240) and COL6A3 (120250) to form disulfide-bonded monomers, but further assembly into dimers and tetramers was prevented, and molecules containing the mutant chain were not secreted. This triple-helical deletion thus resulted in production of half the normal amount of collagen VI.

Pan et al. (2003) identified the IVS14+1G-A transition in a 6-year-old boy with a relatively mild congenital muscular dystrophy phenotype with distal joint hyperlaxity but no joint contractures characteristic Bethlem myopathy. Because the patient was young and could still develop contractures, Pan et al. (2003) concluded that his phenotype could be compatible with sporadic Bethlem myopathy.

Lucioli et al. (2005) identified the IVS14+1G-A mutation in 6 of 16 unrelated patients with Bethlem myopathy and mutations in the COL6A1 gene.

Baker et al. (2007) identified the IVS14+1G-A mutation in 2 additional patients with Bethlem myopathy. Studies showed undisulfide-bonded collagen VI in cell culture medium, suggesting that some structurally abnormal protein was secreted.