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Mutation spectrum of COL1A1/COL1A2 screening by high-resolution melting analysis of Chinese patients with osteogenesis imperfecta.
J Bone Miner Metab. 2020 Mar; 38(2):188-197.JB

Abstract

High-resolution melting (HRM) analysis has been shown to be a time-saving method for the screening of genetic variants. To increase the precision of the diagnosis of osteogenesis imperfecta (OI), we used HRM to explore COL1A1/COL1A2 mutations in 87 Chinese OI patients and to perform population-based studies of the relationships between their genotypes and phenotypes. Peripheral blood samples were collected from the 87 non-consanguineous probands. The coding regions and exon boundaries of COL1A1/COL1A2 were detected by HRM and confirmed by Sanger sequencing. The functional effects of mutations were predicted through bioinformatic tools. Mutations were detected in 70.3% of familial cases and 40% of sporadic cases (p < 0.01). Compared with COL1A1 mutations, patients with COL1A2 mutations were more prone to severe phenotypes. Helical mutations (caused by substitution of the glycine within the Gly-X-Y triplet domain) were more likely to occur in patients with type III and IV (p < 0.05). Haploinsufficiency mutations (caused by frameshift, nonsense, and splice-site mutations) appeared more frequently in patients with type I (p < 0.05). Compared with the Sanger sequencing and whole exome sequencing (WES), HRM was found to reduce total costs by 78%- 80% in patients who had a positive HRM separate melting curve. Our findings suggest that HRM would greatly benefit small and understaffed hospitals and laboratories, and would facilitate the accurate diagnosis and early treatment of OI in remote and less developed regions.

Authors+Show Affiliations

Department of Genetics, Tianjin Medical University, Tianjin, 300070, People's Republic of China.Department of Medical Laboratory, Tianjin Hospital, Tianjin, 300000, People's Republic of China.Colorectal Surgery, Tianjin People's Hospital, Tianjin, 300000, People's Republic of China.School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, People's Republic of China.School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, People's Republic of China.School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, People's Republic of China.Department of Medical Laboratory, Tianjin Hospital, Tianjin, 300000, People's Republic of China.Department of Medical Laboratory, Tianjin Hospital, Tianjin, 300000, People's Republic of China.Orthopedic Ward III, Wuqing People's Hospital, Tianjin, 300000, People's Republic of China.Department of Genetics, Tianjin Medical University, Tianjin, 300070, People's Republic of China.Department of Medical Laboratory, Tianjin Hospital, Tianjin, 300000, People's Republic of China.Department of Genetics, Tianjin Medical University, Tianjin, 300070, People's Republic of China. lig@tmu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31414283

Citation

Ju, Mingyan, et al. "Mutation Spectrum of COL1A1/COL1A2 Screening By High-resolution Melting Analysis of Chinese Patients With Osteogenesis Imperfecta." Journal of Bone and Mineral Metabolism, vol. 38, no. 2, 2020, pp. 188-197.
Ju M, Bai X, Zhang T, et al. Mutation spectrum of COL1A1/COL1A2 screening by high-resolution melting analysis of Chinese patients with osteogenesis imperfecta. J Bone Miner Metab. 2020;38(2):188-197.
Ju, M., Bai, X., Zhang, T., Lin, Y., Yang, L., Zhou, H., Chang, X., Guan, S., Ren, X., Li, K., Wang, Y., & Li, G. (2020). Mutation spectrum of COL1A1/COL1A2 screening by high-resolution melting analysis of Chinese patients with osteogenesis imperfecta. Journal of Bone and Mineral Metabolism, 38(2), 188-197. https://doi.org/10.1007/s00774-019-01039-3
Ju M, et al. Mutation Spectrum of COL1A1/COL1A2 Screening By High-resolution Melting Analysis of Chinese Patients With Osteogenesis Imperfecta. J Bone Miner Metab. 2020;38(2):188-197. PubMed PMID: 31414283.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutation spectrum of COL1A1/COL1A2 screening by high-resolution melting analysis of Chinese patients with osteogenesis imperfecta. AU - Ju,Mingyan, AU - Bai,Xue, AU - Zhang,Tianke, AU - Lin,Yunshou, AU - Yang,Li, AU - Zhou,Huaiyu, AU - Chang,Xiaoli, AU - Guan,Shizhen, AU - Ren,Xiuzhi, AU - Li,Keqiu, AU - Wang,Yi, AU - Li,Guang, Y1 - 2019/08/14/ PY - 2018/08/09/received PY - 2019/07/24/accepted PY - 2019/8/16/pubmed PY - 2020/6/11/medline PY - 2019/8/16/entrez KW - COL1A1/COL1A2 KW - Chinese KW - HRM KW - Osteogenesis imperfecta KW - Phenotypes SP - 188 EP - 197 JF - Journal of bone and mineral metabolism JO - J Bone Miner Metab VL - 38 IS - 2 N2 - High-resolution melting (HRM) analysis has been shown to be a time-saving method for the screening of genetic variants. To increase the precision of the diagnosis of osteogenesis imperfecta (OI), we used HRM to explore COL1A1/COL1A2 mutations in 87 Chinese OI patients and to perform population-based studies of the relationships between their genotypes and phenotypes. Peripheral blood samples were collected from the 87 non-consanguineous probands. The coding regions and exon boundaries of COL1A1/COL1A2 were detected by HRM and confirmed by Sanger sequencing. The functional effects of mutations were predicted through bioinformatic tools. Mutations were detected in 70.3% of familial cases and 40% of sporadic cases (p < 0.01). Compared with COL1A1 mutations, patients with COL1A2 mutations were more prone to severe phenotypes. Helical mutations (caused by substitution of the glycine within the Gly-X-Y triplet domain) were more likely to occur in patients with type III and IV (p < 0.05). Haploinsufficiency mutations (caused by frameshift, nonsense, and splice-site mutations) appeared more frequently in patients with type I (p < 0.05). Compared with the Sanger sequencing and whole exome sequencing (WES), HRM was found to reduce total costs by 78%- 80% in patients who had a positive HRM separate melting curve. Our findings suggest that HRM would greatly benefit small and understaffed hospitals and laboratories, and would facilitate the accurate diagnosis and early treatment of OI in remote and less developed regions. SN - 1435-5604 UR - https://www.unboundmedicine.com/medline/citation/31414283/Mutation_spectrum_of_COL1A1/COL1A2_screening_by_high_resolution_melting_analysis_of_Chinese_patients_with_osteogenesis_imperfecta_ L2 - https://dx.doi.org/10.1007/s00774-019-01039-3 DB - PRIME DP - Unbound Medicine ER -