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A novel mutation in COL2A1 leading to spondyloepiphyseal dysplasia congenita in a three-generation family

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Abstract

Purpose

To investigate the genotype of COL2A1 in a three-generation spondyloepiphyseal dysplasia congenita (SEDC) family.

Methods

Five affected individuals from a Chinese SEDC family were enrolled in the study. All patients underwent thorough physical and radiographic examinations. DNA samples of the affected patients and the healthy controls were collected with the informed consent obtained from each participant. Two short tandem repeat polymorphic markers flanking COL2A1 gene region were detected to determine the haplotype of each patient. Subsequently, sequence analysis was performed in COL2A1 gene to identify potential genetic mutation.

Results

Haplotype analysis showed that the same disease-associated haplotype was segregated through the whole pedigree. A maximum LOD score of 1.5 was obtained with D12S85 and D12S368. DNA sequence analysis revealed a c.1636 G/A transition in exon 25 of the COL2A1 gene, which converted the codon GGT for glycine at position 546 to AGT, a codon for serine. The patients were all heterozygous for the mutation G546S, which was absent in either of the unaffected family members or of the normal individuals.

Conclusions

This is the first familial report of G546S mutation in the COL2A1 gene that results in SEDC. Although great achievements have been made in the recognition of the mutation spectrum, more intensive studies are warranted to further identify correlations between genotype and phenotype.

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References

  1. Spranger JW, Wiedemann HR (1966) Dysplasia spondyloepiphysaria congenita. Helv Paediatr Acta 21:598

    Google Scholar 

  2. 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 

  3. Morita M, Miyamoto K, Nishimoto H, Hosoe H, Shimizu K (2005) Thoracolumbar kyphosing scoliosis associated with spondyloepiphyseal dysplasia congenita: a case report. Spine J 5:217–220

    Article  PubMed  Google Scholar 

  4. Turner LM, Steffensen TS, Leroy J, Gilbert-Barness E (2010) Spondyloepiphyseal dysplasia congenita. Fetal Pediatr Pathol 29:57–62

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. 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 Genet 56:388–395

    CAS  PubMed Central  PubMed  Google Scholar 

  10. 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

    Article  CAS  PubMed  Google Scholar 

  11. 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

    Article  CAS  PubMed  Google Scholar 

  12. 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

    Article  CAS  PubMed  Google Scholar 

  13. 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  PubMed  Google Scholar 

  14. 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

    Article  CAS  PubMed  Google Scholar 

  15. Donahue LR, Chang B, Mohan S, Miyakoshi N, Wergedal JE, Baylink DJ, Hawes NL, Rosen CJ, Ward-Bailey P, Zheng QY, Bronson RT, Johnson KR, Davisson MT (2003) A missense mutation in the mouse Col2a1 gene causes spondyloepiphyseal dysplasia congenita, hearing loss, and retinoschisis. J Bone Miner Res 18:1612–1621

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Elliott AM, Bocangel P, Reed MH, Greenberg CR (2010) A novel COMP mutation in an Inuit patient with pseudoachondroplasia and severe short stature. Genet Mol Res 9:1785–1790

    Article  CAS  PubMed  Google Scholar 

  17. Rozen S, Skaletsky H (2000) Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132:365–386

    CAS  PubMed  Google Scholar 

  18. Vikkula M, Metsaranta M, Ala-Kokko L (1994) Type II collagen mutations in rare and common cartilage diseases. Ann Med 26:107–114

    Article  CAS  PubMed  Google Scholar 

  19. Spranger J, Winterpacht A, Zabel B (1994) The type II collagenopathies: a spectrum of chondrodysplasias. Eur J Pediatr 153:56–65

    CAS  PubMed  Google Scholar 

  20. Freisinger P, Bonaventure J, Stoess H, Pontz BF, Emmrich P, Nerlich A (1996) Type II collagenopathies: are there additional family members? Am J Med Genet 63:137–143

    Article  CAS  PubMed  Google Scholar 

  21. Warman ML, Cormier-Daire V, Hall C, Krakow D, Lachman R, LeMerrer M, Mortier G, Mundlos S, Nishimura G, Rimoin DL, Robertson S, Savarirayan R, Sillence D, Spranger J, Unger S, Zabel B, Superti-Furga A (2011) Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A 155A:943–968

    Article  PubMed  Google Scholar 

  22. Anderson IJ, Goldberg RB, Marion RW, Upholt WB, Tsipouras P (1990) Spondyloepiphyseal dysplasia congenita: genetic linkage to type II collagen (COL2AI). Am J Hum Genet 46:896–901

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Godfrey M, Hollister DW (1988) Type II achondrogenesis-hypochondrogenesis: identification of abnormal type II collagen. Am J Hum Genet 43:904–913

    CAS  PubMed Central  PubMed  Google Scholar 

  24. 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  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  26. Freisinger P, Ala-Kokko L, LeGuellec D, Franc S, Bouvier R, 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  PubMed  Google Scholar 

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Conflict of interest statement

None of the authors has any potential conflict of interest.

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Authors and Affiliations

  1. Department of Spine Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China

    Leilei Xu, Xusheng Qiu, Zezhang Zhu & Yong Qiu

  2. Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, 22 Hankou Road, Nanjing, 210093, Jiangsu, China

    Long Yi

Authors
  1. Leilei Xu
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  2. Xusheng Qiu
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  3. Zezhang Zhu
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  4. Long Yi
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  5. Yong Qiu
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Corresponding authors

Correspondence to Long Yi or Yong Qiu.

Additional information

L. Xu and X. Qiu contributed equally to the study.

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Xu, L., Qiu, X., Zhu, Z. et al. A novel mutation in COL2A1 leading to spondyloepiphyseal dysplasia congenita in a three-generation family. Eur Spine J 23 (Suppl 2), 271–277 (2014). https://doi.org/10.1007/s00586-014-3292-0

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  • DOI: https://doi.org/10.1007/s00586-014-3292-0

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