Uncommon IFITM5 mutation associated with severe skeletal deformity in osteogenesis imperfecta

Osteogenesis imperfecta (OI) is the most common skeletal dysplasia, which predisposes to recurrent fractures and bone deformity and presents with wide clinical variability. More than 80% of OI cases are related to dominantly inherited mutations in COL1A1 or COL1A2. The rest of the cases, however, involve many other noncollagen genes, all of which are autosomal-recessively inherited, except for IFITM5 and WNT1, which are also associated with autosomal dominant OI. Since 2012, a single recurrent heterozygous mutation in IFITM5 (c.-14C>T) has been shown to underlie OI type V. Although this is the most common OI-causing mutation in IFITM5, a second, less common mutation in IFITM5, c.119C>T (p.Ser40Leu), has been identified, which is not associated with the OI type V phenotype. In this report, we describe the clinical and radiological features of a further patient with this uncommon mutation in IFITM5 (c.119C>T, p.Ser40Leu). The patient presented with prenatal signs of severe OI and developed extreme short stature with short and bowed limbs, relative macrocephaly, scoliosis, vertebral compression, and a hypoplastic thorax. He had global developmental delay, recurrent respiratory problems, and required special family care and multidisciplinary treatment. To date, all patients with the uncommon c.119C>T mutation have presented with severe OI, rather than OI type V. Thus, this report further strengthens the case for a genotype-phenotype correlation for IFITM5-related OI.