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, S., McInerney-Leo, A.M., McKenzie, F.A., Baynam, G., Broley, S., Cavan, B.V., Munns, C.F., Pruijs, J.E., Sillence, D., Terhal, P.A., Pryce, K., Brown, M.A., Zankl, A., Thomas, G. and Duncan, E.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 (1). p. 107.

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.

Item Type:	Journal Article
Publisher:	BioMed Central
Copyright:	© 2014 Lazarus et al.
URI:	http://researchrepository.murdoch.edu.au/id/eprint/25083

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