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 Lazarus, Aideen M McInerney-Leo, Fiona A McKenzie, Gareth Baynam, Stephanie Broley, Barbra V Cavan, Craig F Munns, Johannes Egbertus Hans Pruijs, David Sillence, Paulien A Terhal, Karena Price, Matthew A Brown, Andreas Zankl, Gethin Thomas, Emma L Duncan

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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.Method: 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.

    Original languageEnglish
    Article number107
    Pages (from-to)1-6
    Number of pages6
    JournalBMC Musculoskeletal Disorders
    Volume15
    Issue number107
    DOIs
    Publication statusPublished - 2014

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