A new gene for brittle bone disease

Osteogenesis imperfecta also known as brittle bone disease is a human genetic bone disorder affecting 6 to 7 per 100,000 people worldwide and characterized by extremely fragile bones and teeth. Most cases are caused by mutations in two genes encoding different subunits of the collagen type I molecule. Several hundred mutations in these two genes have been described, most as dominant forms. The maturation and the correct folding of collagens is complicated and involves a large number of accessory proteins. Recently mutations in two of these proteins were found in patients with recessive forms. This disease also occurs in dogs, it has been described in Golden Retrievers, Beagles, Collies, Poodles, Norwegian Elkhounds, and Bedlington Terriers. In Golden Retrievers and Beagles mutations in the two genes implied in the synthesis of collagen type I have also been discovered, for other canine cases the underlying genetic defect has not yet been elucidated. Here several rough-coated Dachshunds showed a similar disease inherited as a monogenic autosomal recessive trait. Among DNA segments perfectly shared by the five affected dogs there was the SERPINH1 gene known to be involved in collagen maturation. The sequence of this gene in healthy and affected Dachshunds showed a single mutation exclusively shared by all affected dogs but not by healthy controls. So this mutation is most likely responsible for the disease. The knowledge of this mutation enables genetic testing and will allow breeders to eradicate the deleterious allele from the Dachshund population. SERPINH1 mutations might also be responsible for some human forms, where the causative mutation has not yet been identified.

Original article:
Drögemüller C et al. A missense mutation in the SERPINH1 gene in Dachshunds with osteogenesis imperfecta. PLoS Genet. 2009 5(7):e1000579.