ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2019
Comprehensive genetic analyses using targeted next-generation sequencing and genotype-phenotype correlations in 53 Japanese patients with osteogenesis imperfecta.
Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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16 citing papers in PubMed, 22 citations in OpenAlex.
- Baseline Characteristics of the TOPaZ Study: Randomised Trial of Teriparatide and Zoledronic Acid Compared with Standard Care in Adults with Osteogenesis Imperfecta.Calcified tissue international · 2025Trial
- Dose matters: haploinsufficiency in osteogenesis imperfecta.Nature reviews. Endocrinology · 2026Review
- Pathogenesis and precision management of osteogenesis imperfecta: from genetic mechanisms to novel therapies.World journal of pediatrics : WJP · 2026Review
- Clinical and Genetic Characterization of Osteogenesis Imperfecta in Japanese Patients: Outcomes of Sequential Bisphosphonate Therapy.Calcified tissue international · 2026Article
- Osteogenesis Imperfecta with a gross deletion including theBone reports · 2026Article
- Identification and functional characterization of a novel pathogenicFrontiers in genetics · 2026Article
- Genotype and Phenotype of 198 Korean Patients With Nonlethal Osteogenesis Imperfecta: A Retrospective Cohort Study.Human mutation · 2026Article
- Messenger RNA therapy in bone and joint diseases: Rationale, delivery systems, and applications.Biomaterials translational · 2026Article
- Article
- Characterization of a Novel Col1a1Calcified tissue international · 2025Article
- The patient clinical journey and socioeconomic impact of osteogenesis imperfecta: a systematic scoping review.Orphanet journal of rare diseases · 2023Article
- Osteogenesis imperfecta: a cross-sectional study of skeletal and extraskeletal features in a large cohort of Italian patients.Frontiers in endocrinology · 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
- Genetic analysis in Japanese patients with osteogenesis imperfecta: Genotype and phenotype spectra in 96 probands.Molecular genetics & genomic medicine · 2021Article
- Clinical and genetic analysis in 185 Chinese probands of osteogenesis imperfecta.Journal of bone and mineral metabolism · 2021Article
- 4-Phenylbutyric acid enhances the mineralization of osteogenesis imperfecta iPSC-derived osteoblasts.The Journal of biological chemistryArticle
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To elucidate mutation spectrum and genotype-phenotype correlations in Japanese patients with OI, we conducted comprehensive genetic analyses using NGS, as this had not been analyzed comprehensively in this patient population. Most mutations were located on COL1A1 and COL1A2. Glycine substitutions in COL1A1 resulted in the severe phenotype.
introductionMost cases of osteogenesis imperfecta (OI) are caused by mutations in COL1A1 or COL1A2, which encode α chains of type I collagen. However, mutations in at least 16 other genes also cause OI. The mutation spectrum in Japanese patients with OI has not been comprehensively analyzed, as it is difficult to identify using classical Sanger sequencing. In this study, we aimed to reveal the mutation spectrum and genotype-phenotype correlations in Japanese patients with OI using next-generation sequencing (NGS).
methodsWe designed a capture panel for sequencing 15 candidate OI genes and 19 candidate genes that are associated with bone fragility or Wnt signaling. Using NGS, we examined 53 Japanese patients with OI from unrelated families.
resultsPathogenic mutations were detected in 43 out of 53 individuals. All mutations were heterozygous. Among the 43 individuals, 40 variants were identified including 15 novel mutations. We found these mutations in COL1A1 (n = 30, 69.8%), COL1A2 (n = 12, 27.9%), and IFITM5 (n = 1, 2.3%). Patients with glycine substitution on COL1A1 had a higher frequency of fractures and were more severely short-statured. Although no significant genotype-phenotype correlation was observed for bone mineral density, the trabecular bone score was significantly lower in patients with glycine substitutions.
conclusionWe identified pathogenic mutations in 81% of our Japanese patients with OI. Most mutations were located on COL1A1 and COL1A2. This study revealed that glycine substitutions on COL1A1 resulted in the severe phenotype among Japanese patients with OI.
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