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Phenotypic Variability of Osteogenesis Imperfecta Type V Caused by an IFITM 5 Mutation
Author(s) -
Shapiro Jay R,
Lietman Caressa,
Grover Monica,
Lu James T,
Nagamani Sandesh CS,
Dawson Brian C,
Baldridge Dustin M,
Bainbridge Matthew N,
Cohn Dan H,
Blazo Maria,
Roberts Timothy T,
Brennen FengShu,
Wu Yimei,
Gibbs Richard A,
Melvin Pamela,
Campeau Philippe M,
Lee Brendan H
Publication year - 2013
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.1891
Subject(s) - osteogenesis imperfecta , interosseous membrane , mutation , phenotype , genetics , dentinogenesis imperfecta , sanger sequencing , osteosclerosis , medicine , biology , forearm , pathology , gene
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.