Osteogenesis imperfecta without features of type V caused by a mutation in the IFITM5 gene

Authors

  • Monica Grover,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
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  • Philippe M Campeau,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
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  • Caressa Dee Lietman,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
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  • James T Lu,

    1. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA
    2. Department of Structural and Computational Biology & Molecular Biophysics, Baylor College of Medicine, Houston, TX, USA
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  • Richard A Gibbs,

    1. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA
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  • Alan E Schlesinger,

    1. Department of Radiology, Texas Children's Hospital and Baylor College of Medicine, Houston, TX, USA
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  • Brendan H Lee

    Corresponding author
    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
    2. Howard Hughes Medical Institute, Houston, TX, USA
    • Address correspondence to: Brendan Lee, MD, PhD, Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, R814, MS225, Houston, TX 77030, USA. E-mail: blee@bcm.edu

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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. © 2013 American Society for Bone and Mineral Research.

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