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.
| Autor: | Lazarus S, McInerney-Leo AM, McKenzie FA, Baynam G, Broley S, Cavan BV, Munns CF, Pruijs JE, Sillence D, Terhal PA, Pryce K, Brown MA, Zankl A, Thomas G, Duncan EL; The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, QLD 4102, Australia. e.duncan@uq.edu.au. |
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| Jazyk: | angličtina |
| Zdroj: | BMC musculoskeletal disorders [BMC Musculoskelet Disord] 2014 Mar 27; Vol. 15, pp. 107. Date of Electronic Publication: 2014 Mar 27. |
| DOI: | 10.1186/1471-2474-15-107 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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