Recessive form of brittle bone disease discovered

American scientists have identified a new form of the brittle bone disorder osteogenesis imperfecta and have determined the genetic defect that underlies it.

Osteogenesis imperfecta (OI) is a disorder characterised by bones that break easily and is caused by mutations in the gene encoding the protein type I collagen. The classical form of OI is a dominant disease, meaning that a mutation in only one copy of the type I collagen gene is sufficient to cause the disease.

Joan Marini and colleagues from the US National Institute of Child Health and Human Development in Maryland have now identified a new recessive form of the disease, in which mutations of both copies of a gene are required.

Predicting that some forms of OI might be caused by altered forms of proteins that interact with and modify type I collagen, the authors sequenced the gene encoding an enzyme called P3H1 in five individuals with severe or lethal abnormal bone development.

Mutations that either significantly reduced or eliminated the amount of P3H1 were found in all five individuals. P3H1 chemically modifies a single amino acid in type I collagen, which presumably facilitates folding and promotes stability.

This recessive form of OI has features that overlap with those of classical OI, but is also characterised by distinctive features.

The study will appear in the March issue of Nature Genetics.