The clinical features of osteogenesis imperfecta resulting from a non-functional carboxy terminal pro alpha 1(I) propeptide of type I procollagen and a severe deficiency of normal type I collagen in tissues

J Med Genet. 1990 Sep;27(9):545-51. doi: 10.1136/jmg.27.9.545.


The features of a baby with lethal perinatal osteogenesis imperfecta (OI II), owing to a frameshift mutation that resulted in the production of a truncated and functionless carboxy terminal propeptide of the pro alpha 1(I) chain of type I procollagen, were studied. The baby (OI26) was heterozygous for an insertion of a single uridine nucleotide after base pair 4088 of the prepro alpha 1(I) mRNA of type I procollagen. Only normal type I collagen was incorporated into the extracellular matrix of bone and dermis resulting in a type I collagen content of about 20% of control tissues. The baby was born at 35 weeks' gestation and died shortly afterwards. He was small and had the radiographical features most like those of OI IIB. The skeleton was poorly ossified. The ribs were discontinuously beaded and the femora were broad with multiple healed fractures of the diaphyses and metaphyses. Other long bones had broad metaphyses with overmodelled diaphyses. The calvarium contained many hundreds of wormian bones. Histological examination showed grossly deficient endochondral and intramembranous ossification. The bone was of a woven type without evidence of lamellar bone or Haversian systems and the osteoblasts did not mature into osteocytes. The cortex of the femur contained Haversian canals but they were surrounded by loose collagen fibres and a mosaic pattern of woven bone and islands of cartilage. We propose that OI IIB can be sub-classified into two groups, one with helical mutations and both normal and mutant type I collagen in the tissues, and the other with carboxy terminal propeptide mutations and a severe type I collagen deficiency, but without mutant collagen in the tissues.

Publication types

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

MeSH terms

  • Bone and Bones / diagnostic imaging
  • Collagen / deficiency*
  • Frameshift Mutation
  • Humans
  • Infant, Newborn
  • Ossification, Heterotopic / diagnostic imaging
  • Osteogenesis Imperfecta / diagnostic imaging
  • Osteogenesis Imperfecta / etiology
  • Osteogenesis Imperfecta / pathology*
  • Peptide Fragments / genetics*
  • Procollagen / genetics*
  • Radiography


  • Peptide Fragments
  • Procollagen
  • procollagen type I carboxy terminal peptide
  • Collagen