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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...

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Autores principales: Higuchi, Yousuke, Hasegawa, Kosei, Futagawa, Natsuko, Yamashita, Miho, Tanaka, Hiroyuki, Tsukahara, Hirokazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
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
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author Higuchi, Yousuke
Hasegawa, Kosei
Futagawa, Natsuko
Yamashita, Miho
Tanaka, Hiroyuki
Tsukahara, Hirokazu
author_facet Higuchi, Yousuke
Hasegawa, Kosei
Futagawa, Natsuko
Yamashita, Miho
Tanaka, Hiroyuki
Tsukahara, Hirokazu
author_sort Higuchi, Yousuke
collection PubMed
description 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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spelling pubmed-82228512021-06-29 Genetic analysis in Japanese patients with osteogenesis imperfecta: Genotype and phenotype spectra in 96 probands Higuchi, Yousuke Hasegawa, Kosei Futagawa, Natsuko Yamashita, Miho Tanaka, Hiroyuki Tsukahara, Hirokazu Mol Genet Genomic Med Original Articles 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. John Wiley and Sons Inc. 2021-05-03 /pmc/articles/PMC8222851/ /pubmed/33939306 http://dx.doi.org/10.1002/mgg3.1675 Text en © 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Higuchi, Yousuke
Hasegawa, Kosei
Futagawa, Natsuko
Yamashita, Miho
Tanaka, Hiroyuki
Tsukahara, Hirokazu
Genetic analysis in Japanese patients with osteogenesis imperfecta: Genotype and phenotype spectra in 96 probands
title Genetic analysis in Japanese patients with osteogenesis imperfecta: Genotype and phenotype spectra in 96 probands
title_full Genetic analysis in Japanese patients with osteogenesis imperfecta: Genotype and phenotype spectra in 96 probands
title_fullStr Genetic analysis in Japanese patients with osteogenesis imperfecta: Genotype and phenotype spectra in 96 probands
title_full_unstemmed Genetic analysis in Japanese patients with osteogenesis imperfecta: Genotype and phenotype spectra in 96 probands
title_short Genetic analysis in Japanese patients with osteogenesis imperfecta: Genotype and phenotype spectra in 96 probands
title_sort genetic analysis in japanese patients with osteogenesis imperfecta: genotype and phenotype spectra in 96 probands
topic Original Articles
url 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
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