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Uncommon IFITM5 mutation associated with severe skeletal deformity in osteogenesis imperfecta
Author(s) -
Rodriguez Celin Mercedes,
Moosa Shahida,
Fano Virginia
Publication year - 2018
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12275
Subject(s) - osteogenesis imperfecta , macrocephaly , osteochondrodysplasia , medicine , short stature , mutation , scoliosis , deformity , dentinogenesis imperfecta , compound heterozygosity , genetics , pediatrics , pathology , biology , surgery , gene
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.