Journal article
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, Vol.15(1)
2014
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.
Details
- Title
- 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
- Authors/Creators
- S. Lazarus (Author/Creator)A.M. McInerney-Leo (Author/Creator)F.A. McKenzie (Author/Creator)G. Baynam (Author/Creator)S. Broley (Author/Creator)B.V. Cavan (Author/Creator)C.F. Munns (Author/Creator)J.E. Pruijs (Author/Creator)D. Sillence (Author/Creator)P.A. Terhal (Author/Creator)K. Pryce (Author/Creator)M.A. Brown (Author/Creator)A. Zankl (Author/Creator)G. Thomas (Author/Creator)E.L. Duncan (Author/Creator)
- Publication Details
- BMC Musculoskeletal Disorders, Vol.15(1)
- Publisher
- BioMed Central
- Identifiers
- 991005544392707891
- Copyright
- © 2014 Lazarus et al.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- 1 Clinical & Life Sciences
- 1.132 Extracellular Matrix & Cell Differentiation
- 1.132.1065 Collagen Disorders
- Web Of Science research areas
- Orthopedics
- Rheumatology
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- Clinical Medicine