Genetic analysis in Japanese patients with osteogenesis imperfecta: Genotype and phenotype spectra in 96 probands

Yousuke Higuchi, Kosei Hasegawa, Natsuko Futagawa, Miho Yamashita, Hiroyuki Tanaka, Hirokazu Tsukahara

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Background: Osteogenesis imperfecta (OI) is a rare connective-tissue disorder characterized by bone fragility. Approximately 90% of all OI cases are caused by variants in COL1A1 or COL1A2. Additionally, IFITM5 variants are responsible for the unique OI type 5. We previously analyzed COL1A1/2 variants in 22 Japanese families with OI through denaturing high-performance liquid chromatography screening, but our detection rate was low (41%). Methods: To expand the genotype-phenotype correlations, we performed a genetic analysis of COL1A1/2 and IFITM5 in 96 non-consanguineous Japanese OI probands by Sanger sequencing. Results: Of these individuals, 54, 41, and 1 had type 1 (mild), type 2–4 (moderate-to-severe), and type 5 phenotypes, respectively. In the mild group, COL1A1 nonsense and splice-site variants were prevalent (n = 30 and 20, respectively), but there were also COL1A1 and COL1A2 triple-helical glycine substitutions (n = 2 and 1, respectively). In the moderate-to-severe group, although COL1A1 and COL1A2 glycine substitutions were common (n = 14 and 18, respectively), other variants were also detected. The single case of type 5 had the characteristic c.-14C>T variant in IFITM5. Conclusion: These results increase our previous detection rate for COL1A1/2 variants to 99% and provide insight into the genotype-phenotype correlations in OI.

Original languageEnglish
Article numbere1675
JournalMolecular Genetics and Genomic Medicine
Issue number6
Publication statusPublished - Jun 2021


  • COL1A1
  • COL1A2
  • IFITM5
  • Osteogenesis imperfecta
  • variant

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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