ID | 61944 |
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Higuchi, Yousuke
Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hasegawa, Kosei
Department of Pediatrics, Okayama University Hospital
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Futagawa, Natsuko
Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yamashita, Miho
Faculty of Human Life Sciences, Notre Dame Seishin University
Tanaka, Hiroyuki
Department of Pediatrics, Okayama Saiseikai General Hospital
Tsukahara, Hirokazu
Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Abstract | 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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Keywords | COL1A1
COL1A2
IFITM5
Osteogenesis imperfecta
variant
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Note | This is an Accepted Manuscript of an article published by Wiley
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Published Date | 2021-05-03
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Publication Title |
Molecular Genetics & Genomic Medicine
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Publisher | Wiley
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Start Page | e1675
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ISSN | 2324-9269
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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File Version | publisher
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Related Url | isVersionOf https://doi.org/10.1002/mgg3.1675
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License | https://creativecommons.org/licenses/by-nc-nd/4.0/
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