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Genetic analysis in Japanese patients with osteogenesis imperfecta: Genotype and phenotype spectra in 96 probands
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 variant...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222851/ https://www.ncbi.nlm.nih.gov/pubmed/33939306 http://dx.doi.org/10.1002/mgg3.1675 |
Sumario: | 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. |
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