ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2014
A novel IFITM5 mutation in severe atypical osteogenesis imperfecta type VI impairs osteoblast production of pigment epithelium-derived factor.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- A Clinical Perspective on Advanced Developments in Bone Biopsy Assessment in Rare Bone Disorders.Frontiers in endocrinology · 2020Pooled it
- Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017Trial
- Pathogenesis and precision management of osteogenesis imperfecta: from genetic mechanisms to novel therapies.World journal of pediatrics : WJP · 2026Review
- Murine model of high bone mass osteogenesis imperfecta exhibits bone matrix hyper-mineralization, misaligned mineral crystals, and altered osteoblast differentiation.Bone research · 2026Article
- Molecular drivers of osteogenesis imperfecta: a cellular and extracellular collagen disease.Clinical science (London, England : 1979) · 2025Review
- The Role of PEDF in the Eye, Bone, and Nervous and Immune Systems.Pharmaceutics · 2025Review
- Osteogenesis imperfecta: pathogenesis, classification, and treatment.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2025Review
- An inducible mouse model of osteogenesis imperfecta type V reveals aberrant osteogenesis caused by Ifitm5 c.-14C>T mutation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- A Dyadic Nosology for Osteogenesis Imperfecta and Bone Fragility Syndromes 2024.Calcified tissue international · 2024Review
- Skeletal and Non-skeletal Phenotypes in Children with Osteogenesis Imperfecta.Calcified tissue international · 2024Review
- Update on the Genetics of Osteogenesis Imperfecta.Calcified tissue international · 2024Review
- Bone Quality and Mineralization and Effects of Treatment in Osteogenesis Imperfecta.Calcified tissue international · 2024Review
- Article
- Bone Material Properties in Bone Diseases Affecting Children.Current osteoporosis reports · 2023Review
- Genetic variants and altered expression of SERPINF1 confer disease susceptibility in patients with otosclerosis.Journal of human genetics · 2023Article
- Does the c.-14C>T Mutation in the IFITM5 Gene Provide Identical Phenotypes for Osteogenesis Imperfecta Type V? Data from Russia and a Literature ReviewBiomedicines · 2022Article
- Article
- Antagonism Between PEDF and TGF-β Contributes to Type VI Osteogenesis Imperfecta Bone and Vascular Pathogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Specific Characteristic of Hyperplastic Callus in a Larger Cohort of Osteogenesis Imperfecta Type V.Calcified tissue international · 2022Article
- Single-cell resolution of MET- and EMT-like programs in osteoblasts during zebrafish fin regeneration.iScience · 2022Article
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Authors and funding
11 authors at 7 institutions in 2 countries.
Funding
Abstract
Osteogenesis imperfecta (OI) types V and VI are caused, respectively, by a unique dominant mutation in IFITM5, encoding BRIL, a transmembrane ifitm-like protein most strongly expressed in the skeletal system, and recessive null mutations in SERPINF1, encoding pigment epithelium-derived factor (PEDF). We identified a 25-year-old woman with severe OI whose dermal fibroblasts and cultured osteoblasts displayed minimal secretion of PEDF, but whose serum PEDF level was in the normal range. SERPINF1 sequences were normal despite bone histomorphometry consistent with type VI OI and elevated childhood serum alkaline phosphatase. We performed exome sequencing on the proband, both parents, and an unaffected sibling. IFITM5 emerged as the candidate gene from bioinformatics analysis, and was corroborated by membership in a murine bone co-expression network module containing all currently known OI genes. The de novo IFITM5 mutation was confirmed in one allele of the proband, resulting in a p.S40L substitution in the intracellular domain of BRIL but was absent in unaffected family members. IFITM5 expression was normal in proband fibroblasts and osteoblasts, and BRIL protein level was similar to control in differentiated proband osteoblasts on Western blot and in permeabilized mutant osteoblasts by microscopy. In contrast, SERPINF1 expression was decreased in proband osteoblasts; PEDF was barely detectable in conditioned media of proband cells. Expression and secretion of type I collagen was similarly decreased in proband osteoblasts; the expression pattern of several osteoblast markers largely overlapped reported values from cells with a primary PEDF defect. In contrast, osteoblasts from a typical case of type V OI, with an activating mutation at the 5'-terminus of BRIL, have increased SERPINF1 expression and PEDF secretion during osteoblast differentiation. Together, these data suggest that BRIL and PEDF have a relationship that connects the genes for types V and VI OI and their roles in bone mineralization.
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Registered trials
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