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CC BY-NC-ND 4.0 · AJP Rep 2024; 14(03): e215-e223
DOI: 10.1055/a-2388-3190
Case Reports

A De novo Mutation in the COL1A1 Gene Leading to Severe Osteogenesis Imperfecta: Case Report and Review of the Literature

Yurong Lu 
1   Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China
2   Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong First Medical University, Jinan, Shandong, People's Republic of China
,
Yijia Tian
1   Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China
2   Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong First Medical University, Jinan, Shandong, People's Republic of China
,
Jinxiu Liu
3   Testing Center, Yinfeng Medical Laboratory, Jinan, Shandong, People's Republic of China
,
Yifan Wang
3   Testing Center, Yinfeng Medical Laboratory, Jinan, Shandong, People's Republic of China
,
Xietong Wang
1   Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China
2   Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong First Medical University, Jinan, Shandong, People's Republic of China
4   Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital, Qingdao University, Jinan, Shandong, People's Republic of China
› Author Affiliations Funding This study was supported by projects funded by the National Key Research and Development Program of China (2018YFC1002900, 2018YFC1002903, and 2021YFC2701504).
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Abstract

Introduction Osteogenesis imperfecta (OI) is the most common monogenic inherited skeletal dysplasia disorder. Mutations in the COL1A1/COL1A2 gene cause ∼85 to 90% of OI. Studies of cases have demonstrated that missense mutations are the primary cause of OI, with poor prognosis.

Case Description We report the case of a fetus with skeletal abnormalities and subcutaneous edema. Ultrasound imaging revealed suspected skeletal malformations, including hypoplastic long bones of all four limbs, poorly ossified calvarium, unrevealing nasal bones, and generalized subcutaneous edema. Whole-exome sequencing revealed a heterozygous mutation in COL1A1 (c.2174G > T/p.(G725V), NM_000088.3). According to the American College of Medical Genetics and Genomics guidelines, it was determined to be a pathogenic variant and identified as a de novo variant (PS2 + PP3_strong + PM2_supporting), which has not been reported in the HGMD, gnomAD, ClinVar, or other databases. This variation causes a glycine-to-valine substitution at position 725, located within the Gly-Xaa-Yaa repeat in the helical domain of the collagen molecule.

Conclusion The COL1A1 mutation (c.2174G > T/p.(G725V), NM_000088.3) is a novel pathogenic variant of severe OI. Our study expanded the OI COL1A1 gene variation profiles in the Chinese population and provided a theoretical foundation for prenatal diagnosis, genetic counseling, and obstetric management.

Keywords

osteogenesis imperfecta - COL1A1 gene - whole-exome sequencing - prenatal diagnosis

Ethics Approval

The samples used in this study were collected with appropriate informed consent and approval from the Ethics Committee of Shandong Provincial Hospital, affiliated with Shandong First Medical University (LCYJ: NO. 2018-003).


Authors' Contribution

Y.L. and Y.T. wrote the original draft of this manuscript. J.L. and Y.W. visualized the study. X.W. contributed to the conceptualization; methodology; project administration, writing, review, and editing.


Patient Consent

Images and information from individual participants were obtained from the individual's free prior informed consent.


Data Availability

All the data involved in this study are available in the manuscript, tables, and figures.




Publication History

Received: 13 June 2024

Accepted: 04 August 2024

Accepted Manuscript online:
14 August 2024

Article published online:
12 September 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Savarirayan R, Rossiter JP, Hoover-Fong JE. et al; Skeletal Dysplasia Management Consortium. Best practice guidelines regarding prenatal evaluation and delivery of patients with skeletal dysplasia. Am J Obstet Gynecol 2018; 219 (06) 545-562
    CrossrefPubMedGoogle Scholar
  • 2 Glorieux FH, Moffatt P. Osteogenesis imperfecta, an ever-expanding conundrum. J Bone Miner Res 2013; 28 (07) 1519-1522
    CrossrefPubMedGoogle Scholar
  • 3 Forlino A, Marini JC. Osteogenesis imperfecta. Lancet 2016; 387 (10028): 1657-1671
    CrossrefPubMedGoogle Scholar
  • 4 Marini JC, Forlino A, Bächinger HP. et al. Osteogenesis imperfecta. Nat Rev Dis Primers 2017; 3: 17052
    CrossrefPubMedGoogle Scholar
  • 5 Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 1979; 16 (02) 101-116
    CrossrefPubMedGoogle Scholar
  • 6 Byers PH, Krakow D, Nunes ME, Pepin M. American college of medical genetics. Genetic evaluation of suspected osteogenesis imperfecta (OI). Genet Med 2006; 8 (06) 383-388
    CrossrefPubMedGoogle Scholar
  • 7 Sykes B, Ogilvie D, Wordsworth P, Anderson, Jones N. Osteogenesis imperfecta is linked to both type I collagen structural genes. Lancet 1986; 2 (8498) 69-72
    CrossrefPubMedGoogle Scholar
  • 8 Steiner RD, Basel D. COL1A1/2 Osteogenesis imperfecta. In: Adam MP, Everman DB, Mirzaa GM. et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2005
    Google Scholar
  • 9 Pollitt R, McMahon R, Nunn J. et al. Mutation analysis of COL1A1 and COL1A2 in patients diagnosed with osteogenesis imperfecta type I-IV. Hum Mutat 2006; 27 (07) 716
    CrossrefPubMedGoogle Scholar
  • 10 Gauba V, Hartgerink JD. Synthetic collagen heterotrimers: structural mimics of wild-type and mutant collagen type I. J Am Chem Soc 2008; 130 (23) 7509-7515
    CrossrefPubMedGoogle Scholar
  • 11 Xi L, Zhang H, Zhang ZL. Clinical and genetic analysis in 185 Chinese probands of osteogenesis imperfecta. J Bone Miner Metab 2021; 39 (03) 416-422
    CrossrefPubMedGoogle Scholar
  • 12 Maioli M, Gnoli M, Boarini M. et al. Genotype-phenotype correlation study in 364 osteogenesis imperfecta Italian patients. Eur J Hum Genet 2019; 27 (07) 1090-1100
    CrossrefPubMedGoogle Scholar
  • 13 Augusciak-Duma A, Witecka J, Sieron AL. et al. Mutations in the COL1A1 and COL1A2 genes associated with osteogenesis imperfecta (OI) types I or III. Acta Biochim Pol 2018; 65 (01) 79-86
    CrossrefPubMedGoogle Scholar
  • 14 Marini JC, Forlino A, Cabral WA. et al. Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Hum Mutat 2007; 28 (03) 209-221
    CrossrefPubMedGoogle Scholar
  • 15 Mei Y, Zhang H, Zhang Z. Comparing clinical and genetic characteristics of de novo and inherited COL1A1/COL1A2 variants in a large Chinese cohort of osteogenesis imperfecta. Front Endocrinol (Lausanne) 2022; 13: 935905
    CrossrefPubMedGoogle Scholar
  • 16 Zhytnik L, Maasalu K, Duy BH. et al. De novo and inherited pathogenic variants in collagen-related osteogenesis imperfecta. Mol Genet Genomic Med 2019; 7 (03) e559
    CrossrefPubMedGoogle Scholar
  • 17 Milks KS, Hill LM, Hosseinzadeh K. Evaluating skeletal dysplasias on prenatal ultrasound: an emphasis on predicting lethality. Pediatr Radiol 2017; 47 (02) 134-145
    CrossrefPubMedGoogle Scholar
  • 18 Kucińska-Chahwan A, Roszkowski T, Nowakowska B. et al. Extended genetic testing in fetuses with sonographic skeletal system abnormalities. Ultrasound Obstet Gynecol 2022; 59 (05) 660-667
    CrossrefPubMedGoogle Scholar
  • 19 Morello R. Osteogenesis imperfecta and therapeutics. Matrix Biol 2018; 71-72: 294-312
    CrossrefPubMedGoogle Scholar
  • 20 Tournis S, Dede AD. Osteogenesis imperfecta - a clinical update. Metabolism 2018; 80: 27-37
    CrossrefPubMedGoogle Scholar
  • 21 Ji Y, Ikram A, Ma Z, Peppelenbosch MP, Pan Q. Co-occurrence of heterozygous mutations in COL1A1 and SERPINF1 in a high-risk pregnancy complicated by osteogenesis imperfecta. J Genet 2019; 98 (02) 51
    CrossrefPubMedGoogle Scholar
  • 22 Tanner L, Vainio P, Sandell M, Laine J. Novel COL1A1 mutation c.3290G>T associated with severe form of osteogenesis imperfecta in a fetus. Pediatr Dev Pathol 2017; 20 (05) 455-459
    CrossrefPubMedGoogle Scholar
  • 23 Huang H, Liu J, Zhang G. A novel de novo mutation in COL1A1 leading to osteogenesis imperfecta confirmed by zebrafish model. Clin Chim Acta 2021; 517: 133-138
    CrossrefPubMedGoogle Scholar
  • 24 Zhang L, Pan L, Teng Y, Liang D, Li Z, Wu L. Molecular diagnosis for 55 fetuses with skeletal dysplasias by whole-exome sequencing: a retrospective cohort study. Clin Genet 2021; 100 (02) 219-226
    CrossrefPubMedGoogle Scholar
  • 25 Yang K, Liu Y, Wu J. et al. Prenatal cases reflect the complexity of the COL1A1/2 associated osteogenesis imperfecta. Genes (Basel) 2022; 13 (09) 2
    CrossrefPubMedGoogle Scholar
  • 26 Zhuang J, Chen C, Chen Y. et al. Identification of a rare variant of c. 1777G>A (p.G593S) in the COL1A1 gene as the etiology of recurrent osteogenesis imperfecta by whole-exome sequencing. Front Pediatr 2022; 10: 816090
    CrossrefPubMedGoogle Scholar
  • 27 Cao J, Chen A, Tian L, Yan L, Li H, Zhou B. Application of whole exome sequencing in fetal cases with skeletal abnormalities. Heliyon 2022; 8 (07) e09819
    CrossrefPubMedGoogle Scholar
  • 28 Li R, Wang J, Wang L, Lu Y, Wang C. Two novel mutations of COL1A1 in fetal genetic skeletal dysplasia of Chinese. Mol Genet Genomic Med 2020; 8 (03) e1105
    CrossrefPubMedGoogle Scholar
  • 29 Yang Y, Wang M, Wang H. Prenatal trio-based whole exome sequencing in fetuses with abnormalities of the skeletal system. Mol Genet Genomics 2022; 297 (04) 1017-1026
    CrossrefPubMedGoogle Scholar