Mutation spectrum of COL1A1/COL1A2 screening by high-resolution melting analysis of Chinese patients with osteogenesis imperfecta

  • Mingyan Ju
  • Xue Bai
  • Tianke Zhang
  • Yunshou Lin
  • Li Yang
  • Huaiyu Zhou
  • Xiaoli Chang
  • Shizhen Guan
  • Xiuzhi Ren
  • Keqiu Li
  • Yi Wang
  • Guang LiEmail author
Original Article


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.


COL1A1/COL1A2 Osteogenesis imperfecta Phenotypes HRM Chinese 



The authors would like to thank Dr. Ren Xiuzhi and nurse Chen Mei for providing clinical diagnosis and control blood samples.


This study was supported by research grants from National Key R&D Program of China (2017YFC1001904); National Natural Science Foundation of China (21647008); Tianjin Science and Technology Support Program (16YFZCSY00900).

Compliance with ethical standards

Conflict of interest

None of the authors have conflicts of interest.

Ethics approval

Tianjin Hospital ethics committee.

Supplementary material

774_2019_1039_MOESM1_ESM.doc (413 kb)
Supplementary material 1 (DOC 413 kb)


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Copyright information

© The Japanese Society Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  • Mingyan Ju
    • 1
  • Xue Bai
    • 2
  • Tianke Zhang
    • 3
  • Yunshou Lin
    • 4
  • Li Yang
    • 4
  • Huaiyu Zhou
    • 4
  • Xiaoli Chang
    • 2
  • Shizhen Guan
    • 2
  • Xiuzhi Ren
    • 5
  • Keqiu Li
    • 1
  • Yi Wang
    • 2
  • Guang Li
    • 1
    Email author
  1. 1.Department of GeneticsTianjin Medical UniversityTianjinPeople’s Republic of China
  2. 2.Department of Medical LaboratoryTianjin HospitalTianjinPeople’s Republic of China
  3. 3.Colorectal SurgeryTianjin People’s HospitalTianjinPeople’s Republic of China
  4. 4.School of Basic Medical SciencesTianjin Medical UniversityTianjinPeople’s Republic of China
  5. 5.Orthopedic Ward IIIWuqing People’s HospitalTianjinPeople’s Republic of China

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