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, 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 and Duncan, Emma 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, 15 107: 1-6. doi:10.1186/1471-2474-15-107


Author 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.
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
Formatted 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
Journal name BMC Musculoskeletal Disorders   Check publisher's open access policy
ISSN 1471-2474
Publication date 2014-03-27
Sub-type Article (original research)
DOI 10.1186/1471-2474-15-107
Open Access Status DOI
Volume 15
Issue 107
Start page 1
End page 6
Total pages 6
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2015
Language eng
Formatted 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.
Keyword Osteogenesis imperfecta
Interferon-induced transmembrane protein 5 (IFITM5)
Bone-restricted interferon-induced transmembrane protein-like protein (BRIL)
Hyperplastic callus
Radial head dislocation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Mon, 31 Mar 2014, 17:57:09 EST by Dr Gethin Thomas on behalf of UQ Diamantina Institute