Direct sequencing of PCR products derived from cDNAs for the pro alpha 1 and pro alpha 2 chains of type I procollagen as a screening method to detect mutations in patients with osteogenesis imperfecta

Hum Mutat. 1996;7(2):89-99. doi: 10.1002/(SICI)1098-1004(1996)7:2<89::AID-HUMU1>3.0.CO;2-K.


More than 150 mutations in the genes for type I procollagen have been found in unrelated patients with osteogenesis imperfecta (OI), but mutations have been difficult to define in many patients with the mildest forms of the disease. Here, we have used robotically automated sequencing of the cDNAs for type I procollagen to screen for mutations in 12 patients suspected of having nonlethal OI (types I, III, and IV). Single base mutations that changed codons for obligate glycine residues were found in seven of the patients. Altogether, we analyzed 4,379 bp of sequences of both alleles of the pro alpha 1 (I) collagen (8,758 bp of allelic sequences) and 4,200 bp of sequences of both alleles of the pro alpha 2(I) collagen (8,400 bp of allelic) from each patient.

Publication types

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

MeSH terms

  • Adult
  • Alleles
  • Base Sequence
  • Child, Preschool
  • DNA Primers / chemistry
  • Female
  • Fibroblasts
  • Genetic Testing* / economics
  • Genetic Testing* / methods
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Osteogenesis Imperfecta / diagnosis
  • Osteogenesis Imperfecta / genetics*
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Procollagen / chemistry
  • Procollagen / genetics*
  • Sequence Analysis


  • DNA Primers
  • Procollagen