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The IFITM5 mutation c.-14C > T results in an elongated transcript expressed in human bone; and causes varying phenotypic severity of osteogenesis imperfecta type V

Syndia Lazarus123, Aideen M McInerney-Leo1, Fiona A McKenzie45, Gareth Baynam45, Stephanie Broley4, Barbra V Cavan6, Craig F Munns78, Johannes Egbertus Hans Pruijs9, David Sillence108, Paulien A Terhal11, Karena Pryce1, Matthew A Brown1, Andreas Zankl12, Gethin Thomas1 and Emma L Duncan123*

Author Affiliations

1 The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, QLD 4102, Australia

2 UQ Centre for Clinical Research, University of Queensland, Herston, QLD 4029, Australia

3 Department of Endocrinology, Royal Brisbane & Women’s Hospital, Herston, QLD 4029, Australia

4 Genetic Services of Western Australia, Subiaco, WA 6008, Australia

5 School of Paediatrics and Child Health, The University of Western Australia, Crawley, WA 6009, Australia

6 Cebu Institute of Medicine, Cebu City, Cebu 6000, Philippines

7 Bone & Mineral Medicine, Endocrinology, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia

8 Connective Tissue Dysplasia Management Service The Sydney Children’s Hospital Network, Westmead, NSW 2145, Australia

9 Department of Orthopaedics, University Medical Centre Utrecht, 3584 EA Utrecht, The Netherlands

10 Discipline of Genetic Medicine, Sydney Children’s Hospital Clinical School, University of Sydney, Westmead, NSW 2145, Australia

11 Department of Medical Genetics, University Medical Centre Utrecht, 3508 Utrecht, The Netherlands

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BMC Musculoskeletal Disorders 2014, 15:107  doi:10.1186/1471-2474-15-107

Published: 27 March 2014



The genetic mutation resulting in osteogenesis imperfecta (OI) type V was recently characterised as a single point mutation (c.-14C > T) in the 5’ untranslated region (UTR) of IFITM5, a gene encoding a transmembrane protein with expression restricted to skeletal tissue. This mutation creates an alternative start codon and has been shown in a eukaryotic cell line to result in a longer variant of IFITM5, but its expression has not previously been demonstrated in bone from a patient with OI type V.


Sanger sequencing of the IFITM5 5’ UTR was performed in our cohort of subjects with a clinical diagnosis of OI type V. Clinical data was collated from referring clinicians. RNA was extracted from a bone sample from one patient and Sanger sequenced to determine expression of wild-type and mutant IFITM5.


All nine subjects with OI type V were heterozygous for the c.-14C > T IFITM5 mutation. Clinically, there was heterogeneity in phenotype, particularly in the manifestation of bone fragility amongst subjects. Both wild-type and mutant IFITM5 mRNA transcripts were present in bone.


The c.-14C > T IFITM5 mutation does not result in an RNA-null allele but is expressed in bone. Individuals with identical mutations in IFITM5 have highly variable phenotypic expression, even within the same family.

Osteogenesis imperfecta; Interferon-induced transmembrane protein 5 (IFITM5); Bone-restricted interferon-induced transmembrane protein-like protein (BRIL); Hyperplastic callus; Radial head dislocation