Mutations in SERPINF1 cause osteogenesis imperfecta type VI. J Bone Miner Res 2011 Dec;26(12):2798-803
Date
08/10/2011Pubmed ID
21826736Pubmed Central ID
PMC3214246DOI
10.1002/jbmr.487Scopus ID
2-s2.0-81855224919 (requires institutional sign-in at Scopus site) 150 CitationsAbstract
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.
Author List
Homan EP, Rauch F, Grafe I, Lietman C, Doll JA, Dawson B, Bertin T, Napierala D, Morello R, Gibbs R, White L, Miki R, Cohn DH, Crawford S, Travers R, Glorieux FH, Lee BAuthor
Jennifer A. Doll PhD Assistant Professor in the Biomedical Sciences department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Base Sequence
Child
Child, Preschool
DNA Mutational Analysis
Eye Proteins
Female
Humans
Infant
Infant, Newborn
Male
Molecular Sequence Data
Mutation
Nerve Growth Factors
Osteogenesis Imperfecta
Pedigree
Reproducibility of Results
Serpins
