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.

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Abstract

Background

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.

Methods

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.

Conclusions

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®
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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 (http://creativecommons.org/licenses/by/2.0), 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

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