Published in:
Open Access
01-12-2014 | Research 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
Authors:
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 Pryce, Matthew A Brown, Andreas Zankl, Gethin Thomas, Emma L Duncan
Published in:
BMC Musculoskeletal Disorders
|
Issue 1/2014
Login to get access
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.