Journal of Genetics

, 98:51 | Cite as

Co-occurrence of heterozygous mutations in COL1A1 and SERPINF1 in a high-risk pregnancy complicated by osteogenesis imperfecta

  • Yunpeng Ji
  • Aqsa Ikram
  • Zhongren Ma
  • Maikel P. Peppelenbosch
  • Qiuwei PanEmail author
Research Note


Mutations in several genes, including SERPRINF1 and COL1A1, have been associated with the development of osteogenesis imperfecta (OI). Here, we reported the co-occurrence of a rare heterozygous variant (\(\hbox {c.167C}{>}\hbox {G p.Ala56Gly}\)) in SERPRINF1 and a novel heterozygous mutation (\(\hbox {c.1634G}{>}\hbox {A p.Gly545Asp}\)) in COL1A1 in a foetus with a severe form of OI. Bioinformatics modelling revealed that the effect of the mutation on SPERINF1 is neutral. In contrast, the mutation in COL1A1 is deleterious. It is predicted to cause distortion of the \(\upalpha \) (1) chain of the type I collagen and results in structural instability of the protein. Therefore, a novel dominant variant of COL1A1 likely underlies the severe foetal pathology observed, although we do not exclude the possibility that the heterozygous mutations in SERPINF and COL1A1 may interact and co-ordinately cause pathogenesis. This novel COL1A1 mutation is recommended to be included in the diagnostic panels for OI.


COL1A1 gene foetus heterozygous mutation lethal osteogenesis imperfect SERPINF1 gene 



We are grateful to engineer Shiliang Liu from the Beijing Genomics Institute at Shenzhen for his technique support in targeted NGS. This work was supported by the Ministry of Science and Technology Assistance Project Grant (grant number KY201501005); Characteristic discipline of bioengineering construction for the special guide project of the ‘world-class universities and world-class disciplines’ of Northwest Minzu University (grant number 10018703) and Changjiang Scholars and Innovative Research Team in University (grant number IRT_17R88).

Supplementary material

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Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  1. 1.Biomedical Research CenterNorthwest Minzu UniversityLanzhouPeople’s Republic of China
  2. 2.Department of GeneticsInner Mongolia Maternal and Child Care HospitalHohhotPeople’s Republic of China
  3. 3.Erasmus MC Cancer InstituteErasmus MC-University Medical CenterRotterdamThe Netherlands

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