Phenotypic Variability of Osteogenesis Imperfecta Type V Caused by an IFITM5 Mutation

Jay R Shapiro, Caressa Lietman, Monica Grover, James T Lu, Sandesh CS Nagamani, Brian C Dawson, Dustin M Baldridge, Matthew N Bainbridge, Dan H Cohn, Maria Blazo, Timothy T Roberts, Feng‐Shu Brennen, Yimei Wu, Richard A Gibbs, Pamela Melvin, Philippe M Campeau, Brendan H Lee

In a large cohort of osteogenesis imperfecta type V (OI type V) patients (17 individuals from 12 families), we identified the same mutation in the 5' untranslated region (5'UTR) of the interferon-induced transmembrane protein 5 (IFITM5) gene by whole exome and Sanger sequencing (IFITM5 c.-14C > T) and provide a detailed description of their phenotype. This mutation leads to the creation of a novel start codon adding five residues to IFITM5 and was recently reported in several other OI type V families. The variability of the phenotype was quite large even within families. Whereas some patients presented with the typical calcification of the forearm interosseous membrane, radial head dislocation and hyperplastic callus (HPC) formation following fractures, others had only some of the typical OI type V findings. Thirteen had calcification of interosseous membranes, 14 had radial head dislocations, 10 had HPC, 9 had long bone bowing, 11 could ambulate without assistance, and 1 had mild unilateral mixed hearing loss. The bone mineral density varied greatly, even within families. Our study thus highlights the phenotypic variability of OI type V caused by the IFITM5 mutation.