Skip to main content

RETRACTED ARTICLE: Identification of a novel mutation of the COL2A1 gene in a Chinese family with spondyloepiphyseal dysplasia congenita

European Spine Journal volume 24, pages 1813–1819 (2015)Cite this article

This article was retracted on 08 October 2021

This article has been updated

Abstract

Purpose

To identify potential disease-causing mutation in the COL2A1 gene in a Chinese family with autosomal dominant spondyloepiphyseal dysplasia congenita (SEDC) and to analyze the phenotype–genotype correlation.

Methods

Complete physical and radiographic examinations of four affected individuals from SEDC family were conducted. Genomic DNA were isolated from peripheral blood leukocytes. All 54 exons and exon–intron boundaries of the COL2A1 gene were amplified by polymerase chain reaction (PCR) and bidirectionally sequenced.

Results

All four affected individuals were found carried a novel missense mutation of c.2224G>A (p.Gly687Ser) in COL2A1, while normal members of the family and 50 healthy controls did not have this mutation. Protein prediction of missense mutation by polyphen-2 and SIFT software and mutation taster indicated severe damage to the function.

Conclusions

c.2224G>A (p.Gly687Ser) is a novel mutation of COL2A1 associated with spondyloepiphyseal dysplasia congenital. There are heterozygous of phenotype for the mutation in members of the pedigree analyzed. Onset becomes more earlier and severe with each successive generation.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Change history

References

  1. Spranger JW, Langer LO Jr (1970) Spondyloepiphyseal dysplasia congenita. Radiology 94:313–322

    CAS  Article  Google Scholar 

  2. Anderson IJ, Goldberg RB, Marion RW, Upholt WB, Tsipouras P (1990) Spondyloepiphyseal dysplasia congenita: genetic linkage to type 11 collagen (COL2A1). Am J Hum Gene 46:896–901

    CAS  Google Scholar 

  3. Ikegawa S, Iwaya T, Taniguchi K, Kimizuka M (1993) Retinal detachment in spondyloepiphyseal dysplasia congenita. J Pediatr Orthop 13:791–792

    CAS  Article  Google Scholar 

  4. Dahiya R, Cleveland S, Megerian CA (2000) Spondyloepiphyseal dysplasia congenita associated with conductive hearing loss. Ear Nose Throat J 79:178–182

    CAS  Article  Google Scholar 

  5. Tofield CE, Mackinnon CA (2003) Cleft palate repair in spondyloepiphyseal dysplasia congenita: minimizing the risk of cervical cord compression. Cleft Palate Craniofac 40:629–631

    Article  Google Scholar 

  6. Harrod MJ, Friedman JM, Currarino G, Pauli RM, Langer LO Jr (1984) Genetic heterogeneity in spondyloepiphyseal dysplasia congenita. Am J Med Gene 18:311–320

    CAS  Article  Google Scholar 

  7. Tiller GE, Weis MA, Polumbo PA, Gruber HE, Rimoin DL, Cohn DH, Eyre DR (1995) An RNA-splicing mutation (G+5IVS20) in the type II collagen gene (COL2A1) in a family with spondyloepiphyseal dysplasia congenita. Am J Hum Gene 56:388–395

    CAS  Google Scholar 

  8. Unger S, Korkko J, Krakow D, Lachman RS, Rimoin DL, Cohn DH (2001) Double heterozygosity for pseudoachondroplasia and spondyloepiphyseal dysplasia congenita. Am J Med Genet 104:140–146

    CAS  Article  Google Scholar 

  9. Nishimura G, Haga N, Kitoh H, Tanaka Y, Sonoda T, Kitamura M, Shirahama S, Itoh T, Nakashima E, Ohashi H, Ikegawa S (2005) The phenotypic spectrum of COL2A1 mutations. Hum Mutat 26:36–43

    CAS  Article  Google Scholar 

  10. Mark PR, Torres-Martinez W, Lachman RS, Weaver DD (2011) Association of a p.Pro786Leu variant in COL2A1 with mild spondyloepiphyseal dysplasia congenita in a three-generation family. Am J Med Genet A 155A:174–179

    Article  Google Scholar 

  11. Xia X, Cui Y, Huang Y, Pan L, Wu Y, Zhang P, Jin B (2007) A first familial G504S mutation of COL2A1 gene results in distinctive spondyloepiphyseal dysplasia congenita. Clin Chim Acta 382:148–150

    CAS  Article  Google Scholar 

  12. Zhang Z, He JW, Fu WZ, Zhang CQ, Zhang ZL (2011) Identification of three novel mutations in the COL2A1 gene in four unrelated Chinese families with spondyloepiphyseal dysplasia congenita. Biochem Biophys Res Commun 413:504–508

    CAS  Article  Google Scholar 

  13. Chung BH, Luk HM, Lo IF, Lam ST, Li RH (2013) A second report of p.Pro986Leu variant in COL2A1-phenotypic overlap with SEDC and other forms of type II collagenopathies. J Med Genet A 161A:918–920

    Article  Google Scholar 

  14. Xu L, Qiu X, Zhu Z, Yi L, Qiu Y (2014) A novel mutation in COL2A1 leading to spondyloepiphyseal dysplasia congenita in a three-generation family. Eur Spine J 23(Suppl 2):S271–S277

    Article  Google Scholar 

  15. Li S, Zhou H, Qin H, Guo H, Bai Y (2014) A novel mutation in the COL2A1 gene in a Chinese family with Spondyloepiphyseal dysplasia congenita. Joint Bone Spine 81:86–89

    CAS  Article  Google Scholar 

  16. Liu YF, Chen WM, Lin YF, Yang RC, Lin MW, Li LH, Chang YH, Jou YS, Lin PY, Su JS, Huang SF, Hsiao KJ, Fann CS, Hwang HW, Chen YT, Tsai SF (2005) Type II collagen gene variants and inherited osteonecrosis of the femoral head. N Engl J Med 352:2294–2301

    CAS  Article  Google Scholar 

  17. Su P, Li R, Liu S, Zhou Y, Wang X, Patil N, Mow CS, Mason JC, Huang D, Wang Y (2008) Age at onset-Dependent presentations of premature hip osteoarthritis, avascular necrosis of the femoral head, or Legg-Calvé-Perthes disease in a single family, consequent upon a p. Gly1170Ser mutation of COL2A1. Arthritis Rheum 58:1701–1706

    CAS  Article  Google Scholar 

  18. Terhal PA, van Dommelen P, Le Merrer M, Zankl A, Simon ME, Smithson SF, Marcelis C, Kerr B, Kinning E, Mansour S, Hennekam RC, van der Hout AH, Cormier-Daire V, Lund AM, Goodwin L, Mégarbané A, Lees M, Betz RC, Tobias ES, Coucke P, Mortier GR (2012) Mutation-based growth charts for SEDC and other COL2A1 related dysplasias. Am J Med Genet C Semin Med Genet 160C:205–216

    Article  Google Scholar 

  19. Jung SC, Mathew S, Li QW, Lee YJ, Lee KS, Song HR (2004) Spondyloepiphyseal dysplasia congenita with absent femoral head. J Pediatr Orthop B 13:63–69

    PubMed  Google Scholar 

  20. Mortier GR, Weis M, Nuytinck L, King LM, Wilkin DJ, De Paepe A, Lachman RS, Rimoin DL, Eyre DR, Cohn DH (2000) Report of five novel and one recurrent COL2A1 mutations with analysis of genotype-phenotype correlation in patients with a lethal type II collagen disorder. J Med Genet 37:263–271

    CAS  Article  Google Scholar 

  21. Helseth DJ, Veis A (1981) Collagen self-assembly in vitro. Differentiating specific telopeptide-dependent interactions using selective enzyme modification and the addition of free amino telopeptide. J Biol Chem 256:7118–7128

    CAS  Article  Google Scholar 

  22. Sato K, Ebihara T, Adachi E, Kawashima S, Hattori S, Irie S (2000) Possible involvement of amino telopeptide in selfassembly and thermal stability of collagen I as revealed by its removal with proteases. J Biol Chem 275:25870–25875

    CAS  Article  Google Scholar 

  23. Freisinger P, Ala-Kokko L, LeGuellec D, Franc S, Bouvi Ritvaniemi P, Prockop DJ, Bonaventure J (1994) Mutation in the COL2A1 gene in a patient with hypochondrogenesis. Expression of mutated COL2A1 gene is accompanied by expression of genes for type I procollagen in chondrocytes. J Biol Chem 269:13663–13669

    CAS  Article  Google Scholar 

Download references

Acknowledgments

We would like to thank the family members for participating in this study. This work was supported by grants from the National Natural Science Foundation of China (No. 81372871 and No. 81302339) and Shanxi Natural Science Foundation of China (2010011050-4). We also thank the patients and their clinicians for participation in this study.

Conflict of interest

The authors declare that they have no conflicts of interest concerning this article.

Author information

Affiliations

  1. Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan Province, China

    Hongzhuo Li & Tao Xiao

  2. Department of Orthopedics, Heping Hospital Attached to Changzhi Medical College, Changzhi, 046000, Shanxi Province, China

    Hongzhuo Li

  3. Central Laboratory, Heping Hospital Attached to Changzhi Medical College, Changzhi, 046000, Shanxi Province, China

    Liang Ma

  4. Department of Orthopedics, Qinyuan County People’s Hospital, Changzhi, 046000, Shanxi Province, China

    Baozhu Wang

  5. Department of Ophthalmology, Heping Hospital Attached to Changzhi Medical College, Changzhi, 046000, Shanxi Province, China

    Yun Cui

Authors
  1. Hongzhuo Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liang Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Baozhu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yun Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tao Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tao Xiao.

Appendix

Appendix

See Table 2.

Table 2 Sequences of primers for COL2A1 exons
Full size table

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Li, H., Ma, L., Wang, B. et al. RETRACTED ARTICLE: Identification of a novel mutation of the COL2A1 gene in a Chinese family with spondyloepiphyseal dysplasia congenita. Eur Spine J 24, 1813–1819 (2015). https://doi.org/10.1007/s00586-015-3999-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00586-015-3999-6

Keywords

  • Spondyloepiphyseal dysplasia congenita
  • COL2A1
  • Mutation
  • Phenotype