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

Lazarus, Syndia, McInerney-Leo, Aideen M., McKenzie, Fiona A., Baynam, Gareth, Broley, Stephanie, Cavan, Barbra V., Munns, Craig F., Pruijs, Johannes Egbertus Hans, Sillence, David, Terhal, Paulien A., Pryce, Karena, Brown, Matthew A., Zankl, Andreas, Thomas, Gethin, & Duncan, Emma L. (2014) 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. BMC Musculoskeletal Disorders, 15, Article Number:-107.

View at publisher (open access)



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. Results: 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.

Impact and interest:

8 citations in Scopus
5 citations in Web of Science®
Search Google Scholar™

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

Full-text downloads:

19 since deposited on 23 Sep 2015
7 in the past twelve months

Full-text downloads displays the total number of times this work’s files (e.g., a PDF) have been downloaded from QUT ePrints as well as the number of downloads in the previous 365 days. The count includes downloads for all files if a work has more than one.

ID Code: 87640
Item Type: Journal Article
Refereed: Yes
Keywords: Bone-restricted interferon-induced transmembrane protein-like protein (BRIL), Hyperplastic callus, Interferon-induced transmembrane protein 5 (IFITM5), Osteogenesis imperfecta, Radial head dislocation, complementary DNA, protein, protein ifitm 5, RNA, unclassified drug, 5' untranslated region, adolescent, adult, article, autosomal dominant inheritance, body height, bone, bone density, bone fragility, calcification, child, clinical article, disease severity, elbow, female, forearm, gene expression, gene mutation, gene sequence, genetic heterogeneity, heterozygote, human, limb deformity, male, modifier gene, mother, mutant, ossifying myositis, osteogenesis imperfecta type 4, phenotype, physical activity, RNA extraction, son, start codon, transcription elongation, wild type, 5' Untranslated Regions, Bone and Bones, Bony Callus, Calcinosis, Codon, Initiator, Dislocations, DNA, Complementary, Fractures, Spontaneous, Genes, Dominant, Humans, Hyperplasia, Middle Aged, Point Mutation, Radius, RNA, Messenger, Sequence Analysis, DNA
DOI: 10.1186/1471-2474-15-107
ISSN: 1471-2474
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: © 2014 Lazarus et al. al.; licensee BioMed Central Ltd.
Copyright Statement: This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (, which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited.
Deposited On: 23 Sep 2015 04:41
Last Modified: 24 Mar 2016 05:46

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page