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Clinical Trial
. 2013 Jul;28(7):1523-30.
doi: 10.1002/jbmr.1891.

Phenotypic variability of osteogenesis imperfecta type V caused by an IFITM5 mutation

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Free PMC article
Clinical Trial

Phenotypic variability of osteogenesis imperfecta type V caused by an IFITM5 mutation

Jay R Shapiro et al. J Bone Miner Res. 2013 Jul.
Free PMC article

Abstract

In a large cohort of osteogenesis imperfecta type V (OI type V) patients (17 individuals from 12 families), we identified the same mutation in the 5' untranslated region (5'UTR) of the interferon-induced transmembrane protein 5 (IFITM5) gene by whole exome and Sanger sequencing (IFITM5 c.-14C > T) and provide a detailed description of their phenotype. This mutation leads to the creation of a novel start codon adding five residues to IFITM5 and was recently reported in several other OI type V families. The variability of the phenotype was quite large even within families. Whereas some patients presented with the typical calcification of the forearm interosseous membrane, radial head dislocation and hyperplastic callus (HPC) formation following fractures, others had only some of the typical OI type V findings. Thirteen had calcification of interosseous membranes, 14 had radial head dislocations, 10 had HPC, 9 had long bone bowing, 11 could ambulate without assistance, and 1 had mild unilateral mixed hearing loss. The bone mineral density varied greatly, even within families. Our study thus highlights the phenotypic variability of OI type V caused by the IFITM5 mutation.

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Figures

Figure 1
Figure 1
Radiographic features in OI type V. (A, B) Radial head dislocation (arrows on the right) and forearm interosseous membrane calcification (middle arrows) in patients 1 and 3, respectively. (C) HPC in patient 14 at 1.5 years.
Figure 2
Figure 2
Prenatal ultrasound at 22 weeks showing bowing of the femur (the crosshairs show the extremities of the femur).
Figure 3
Figure 3
(A) Pedigrees of the individuals described. (B) Example of Sanger sequencing results for the IFITM5 mutation, here in patient 10 and her parents. (C) Two affected members of the same family: patients 8 and 9. The father is aged 52 years, and the son is 18 years old at the time of the photograph. Although the son was treated at an earlier age with bisphosphonates, this does not explain the important difference in phenotype.

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References

    1. Shapiro JR, Sponsellor PD. Osteogenesis imperfecta: questions and answers. Curr Opin Pediatr. 2009;21(6):709–16. - PubMed
    1. Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979;16(2):101–16. - PMC - PubMed
    1. Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet. 2004;363(9418):1377–85. - PubMed
    1. Glorieux FH, Rauch F, Plotkin H, Ward L, Travers R, Roughley P, Lalic L, Glorieux DF, Fassier F, Bishop NJ. Type V osteogenesis imperfecta: a new form of brittle bone disease. J Bone Miner Res. 2000;15(9):1650–8. - PubMed
    1. Brenner RE, Schiller B, Pontz BF, Lehmann H, Teller WM, Spranger J, Vetter U. [Osteogenesis imperfecta in childhood and adolescence] Monatsschr Kinderheilkd. 1993;141(12):940–5. German. - PubMed

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