Journal Article10.1136/JMEDGENET-2012-101307
Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of the IFITM5 c.−14C>T mutation in all patients
Frank Rauch,Pierre Moffatt,Moira S. Cheung,Peter J. Roughley,Liljana Lalic,Allan M. Lund,Norman Ramirez,Somayyeh Fahiminiya,Jacek Majewski,Francis H. Glorieux +9 more
TL;DR: Even though the disease-causing mutation is identical among patients with OI type V, the interindividual phenotypic variability is considerable.
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Abstract: Background Osteogenesis imperfecta (OI) type V is an autosomal dominant bone fragility disorder that we had described a decade ago. Recent research has shown that OI type V is caused by a recurrent c.-14C>T mutation in IFITM5 . In the present study, we assessed all patients diagnosed with OI type V at our institutions for the presence of the IFITM5 mutation.
Methods IFITM5 exon 1 was analysed by Sanger sequencing in genomic DNA from 42 patients with OI type V (age: 2–67 years; 18 female).
Results The c.−14C>T mutation of IFITM5 was detected in all individuals. Indicators of disease severity varied widely: Height z-scores (n=38) ranged from −8.7 to −0.1, median −3.5. Median final height was 147 cm in men (N=15) and 145 cm in women (N=10). Lumbar spine areal bone mineral density z-scores in the absence of bisphosphonate treatment (n=29) were between −7.7 and −0.7, median −5.3. Scoliosis was present in 57%, vertebral compression fractures in 90% of patients.
Conclusions Even though the disease-causing mutation is identical among patients with OI type V, the interindividual phenotypic variability is considerable.
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Citations
Osteogenesis imperfecta in children and adolescents—new developments in diagnosis and treatment
TL;DR: Newer medications with anti-resorptive and bone anabolic action are being investigated in an attempt to improve on the efficacy of bisphosphonates but the safety and efficacy of these new approaches in children with OI is not yet established.
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Genetic Causes and Mechanisms of Osteogenesis Imperfecta
TL;DR: The known genetic causes of OI, animal models that recapitulate the human disease and mechanisms that underlie disease pathogenesis are summarized and the effects of disrupted collagen networks on extracellular matrix signaling and its impact on disease progression are discussed.
125
Osteogenesis Imperfecta: New Perspectives From Clinical and Translational Research.
Josephine T. Tauer,Marie-Eve Robinson,Frank Rauch +2 more
- 20 Feb 2019
TL;DR: Preclinical studies in OI mouse models have shown encouraging effects when the antiresorptive effect of a bisphosphonate was combined with bone anabolic therapy using a sclerostin antibody.
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Osteogenesis Imperfecta: Mechanisms and signaling pathways connecting classical and rare OI types.
TL;DR: Osteogenesis imperfecta (OI) is a phenotypically and genetically heterogeneous skeletal dysplasia characterized by bone fragility, growth deficiency and skeletal deformity as discussed by the authors.
Zebrafish type I collagen mutants faithfully recapitulate human type I collagenopathies
Charlotte Gistelinck,Charlotte Gistelinck,Ronald Y. Kwon,Fransiska Malfait,Sofie Symoens,Matthew P. Harris,Matthew P. Harris,Katrin Henke,Katrin Henke,Michael Brent Hawkins,Michael Brent Hawkins,Shannon Fisher,Patrick Sips,Brecht Guillemyn,Jan Willem Beck,Petra Vermassen,Hanna De Saffel,Paul Witten,MaryAnn Weis,Anne De Paepe,David R. Eyre,Andy Willaert,Paul Coucke +22 more
TL;DR: The future potential of zebrafish as a tool to further dissect the molecular basis of phenotypic variability in human type I collagenopathies is illustrated to improve diagnostic strategies as well as promote the discovery of new targetable pathways for pharmacological intervention of these disorders.
93
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Type V osteogenesis imperfecta: a new form of brittle bone disease.
Francis H. Glorieux,Francis H. Glorieux,Frank Rauch,Horacio Plotkin,Leanne M Ward,Rose Travers,Peter J. Roughley,Peter J. Roughley,Ljiljana Lalic,Delphine F. Glorieux,François Fassier,Nick Bishop +11 more
TL;DR: OI type V is a new form of autosomal dominant OI, which does not appear to be associated with collagen type I mutations, and the genetic defect underlying this disease remains to be elucidated.
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A Mutation in the 5′-UTR of IFITM5 Creates an In-Frame Start Codon and Causes Autosomal-Dominant Osteogenesis Imperfecta Type V with Hyperplastic Callus
Oliver Semler,Lutz Garbes,Katharina Keupp,Daniel Swan,Katharina Zimmermann,Jutta Becker,Sandra Iden,Brunhilde Wirth,Peer Eysel,Friederike Koerber,Eckhard Schoenau,Stefan K. Bohlander,Stefan K. Bohlander,Bernd Wollnik,Christian Netzer +14 more
TL;DR: In this article, a heterozygous de novo mutation in the 5′-untranslated region of IFITM5 (the gene encoding Interferon induced transmembrane protein 5), 14bp upstream of the annotated translation initiation codon (c.−14C>T).
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