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Mutations in SERPINF1 cause osteogenesis imperfecta type VI
Author(s) -
Homan Erica P,
Rauch Frank,
Grafe Ingo,
Lietman Caressa,
Doll Jennifer A,
Dawson Brian,
Bertin Terry,
Napierala Dobrawa,
Morello Roy,
Gibbs Richard,
White Lisa,
Miki Rika,
Cohn Daniel H,
Crawford Susan,
Travers Rose,
Glorieux Francis H,
Lee Brendan
Publication year - 2011
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.487
Subject(s) - osteogenesis imperfecta , osteoid , genetics , loss function , gene , biology , mutation , fibrodysplasia ossificans progressiva , procollagen peptidase , microbiology and biotechnology , phenotype , anatomy , ossification
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