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- 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
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
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
BONE metabolism; HYPERPLASIA; CALLUS; JOINT dislocations; DNA; SPONTANEOUS fractures; GENES; GENETIC mutation; OSTEOGENESIS imperfecta; RADIAL bone; RNA; PHENOTYPES; BONE density; GENETIC carriers; SEQUENCE analysis; CALCINOSIS; DISEASE complications
- Publication
BMC Musculoskeletal Disorders, 2014, Vol 15, Issue 1, p107
- ISSN
1471-2474
- Publication type
journal article
- DOI
10.1186/1471-2474-15-107