title: Osteogenesis imperfecta without features of type V caused by a mutation in the IFITM5 gene.
abstract: Osteogenesis imperfecta (OI) is typically caused by mutations in type 1 collagen genes, but in recent years new recessive and dominant forms caused by mutations in a plethora of different genes have been characterized. OI type V is a dominant form caused by the recurrent (c.-14C > T) mutation in the 5'UTR of the IFITM5 gene. The mutation adds five residues to the N-terminus of the IFITM5, but the pathophysiology of the disease remains to be elucidated. Typical clinical features present in the majority of OI type V patients include interosseous membrane calcification between the radius and ulna and between the tibia and fibula, radial head dislocation, and significant hyperplastic callus formation at the site of fractures. We report a 5-year-old child with clinical features of OI type III or severe OI type IV (characteristic facies, gray sclerae, typical fractures) and absence of classical features of OI type V with a de novo recurrent IFITM5 mutation (c.-14C > T), now typical of OI type V. This highlights the variability of OI caused by IFITM5 mutations and suggests screening for mutations in this gene in most cases of OI where type 1 collagen mutations are absent.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Grover
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Campeau
authors.forename: Caressa Dee
authors.initials: CD
authors.lastname: Lietman
authors.forename: James T
authors.initials: JT
authors.lastname: Lu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Alan E
authors.initials: AE
authors.lastname: Schlesinger
authors.forename: Brendan H
authors.initials: BH
authors.lastname: Lee
mesh_terms: D001483:Base Sequence; D002648:Child; D005260:Female; D005542:Forearm / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree; D011859:Radiography
chemical_list: C575746:IFITM5 protein, human; D008565:Membrane Proteins
keywords: HYPERPLASTIC CALLUS; IFITM5; INTEROSSEOUS MEMBRANE CALCIFICATION; OSTEOGENESIS IMPERFECTA; TYPE V; WHOLE EXOME SEQUENCING