TY - JOUR
T1 - Genetic analysis in Japanese patients with osteogenesis imperfecta
T2 - Genotype and phenotype spectra in 96 probands
AU - Higuchi, Yousuke
AU - Hasegawa, Kosei
AU - Futagawa, Natsuko
AU - Yamashita, Miho
AU - Tanaka, Hiroyuki
AU - Tsukahara, Hirokazu
N1 - Funding Information:
The authors thank the patients and their family members who participated in this study. We also thank the institutions involved for their collaboration in the collection of the samples and clinical data. This study was supported in part by a Grant‐in‐Aid for Scientific Research (No. 23791177) from the Japan Society for the Promotion of Science, a Grant‐in‐Aid for Health Labor Sciences Research (No. 201128153B and 201324078B) from the Ministry of Health, Labor and Welfare of Japan, and a Grant‐in‐Aid for Practical Research Project for Rare/Intractable Diseases (No. 16ek0109135h0002) from the Japan Agency for Medical Research and Development.
Funding Information:
Grant‐in‐Aid for Scientific Research (No. 23791177) from the Japan Society for the Promotion of Science. Grant‐in‐Aid for Health Labor Sciences Research (No. 201128153B and 201324078B) from the Ministry of Health, Labor and Welfare of Japan. Grant‐in‐Aid for Practical Research Project for Rare/Intractable Diseases (No. 16ek0109135h0002) from the Japan Agency for Medical Research and Development.
Publisher Copyright:
© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - COL1A1
KW - COL1A2
KW - IFITM5
KW - Osteogenesis imperfecta
KW - variant
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U2 - 10.1002/mgg3.1675
DO - 10.1002/mgg3.1675
M3 - Article
C2 - 33939306
AN - SCOPUS:85104931845
VL - 9
JO - Molecular genetics & genomic medicine
JF - Molecular genetics & genomic medicine
SN - 2324-9269
IS - 6
M1 - e1675
ER -