| Affiliation: | 1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA;2. Genetics Unit, Shriners Hospital for Children and McGill University, Montréal, Québec, Canada;3. Department of Surgery, NorthShore University Health System Research Institute, Evanston, IL, USA;4. Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA;5. Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA;6. Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, CA, USA;7. International Skeletal Dysplasia Registry, Cedars‐Sinai Medical Center, Los Angeles, CA, USA;8. Howard Hughes Medical Institute, Houston, TX, USA |
| Abstract: | Osteogenesis imperfecta (OI) is a spectrum of genetic disorders characterized by bone fragility. It is caused by dominant mutations affecting the synthesis and/or structure of type I procollagen or by recessively inherited mutations in genes responsible for the posttranslational processing/trafficking of type I procollagen. Recessive OI type VI is unique among OI types in that it is characterized by an increased amount of unmineralized osteoid, thereby suggesting a distinct disease mechanism. In a large consanguineous family with OI type VI, we performed homozygosity mapping and next‐generation sequencing of the candidate gene region to isolate and identify the causative gene. We describe loss of function mutations in serpin peptidase inhibitor, clade F, member 1 (SERPINF1) in two affected members of this family and in an additional unrelated patient with OI type VI. SERPINF1 encodes pigment epithelium–derived factor. Hence, loss of pigment epithelium–derived factor function constitutes a novel mechanism for OI and shows its involvement in bone mineralization. © 2011 American Society for Bone and Mineral Research |
