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05.04.2023 | Research

Identification of DSPP novel variants and phenotype analysis in dentinogenesis dysplasia Shields type II patients

verfasst von: Qin Du, Li Cao, Nana Yan, Sujun Kang, Mu Lin, Peilin Cao, Ran Jia, Chenyang Wang, Hanyu Qi, Yue Yu, Jing Zou, Jiyun Yang

Erschienen in: Clinical Oral Investigations | Ausgabe 7/2023

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Abstract

Objectives

To investigate the genetic causes and teeth characteristics of dentin dysplasia Shields type II(DD-II) in three Chinese families.

Materials and methods

Data from three Chinese families affected with DD-II were collected. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were conducted to screen for variations, and Sanger sequencing was used to verify mutation sites. The physical and chemical characteristics of the affected teeth including tooth structure, hardness, mineral content, and ultrastructure were investigated.

Results

A novel frameshift deletion mutation c.1871_1874del(p.Ser624fs) in DSPP was found in families A and B, while no pathogenic mutation was found in family C. The affected teeth’s pulp cavities were obliterated, and the root canals were smaller than normal teeth and irregularly distributed comprising a network. The patients’ teeth also had reduced dentin hardness and highly irregular dentinal tubules. The Mg content of the teeth was significantly lower than that of the controls, but the Na content was obviously higher than that of the controls.

Conclusions

A novel frameshift deletion mutation, c.1871_1874del (p.Ser624fs), in the DPP region of the DSPP gene causes DD-II. The DD-II teeth demonstrated compromised mechanical properties and changed ultrastructure, suggesting an impaired function of DPP. Our findings expand the mutational spectrum of the DSPP gene and strengthen the understanding of clinical phenotypes related to the frameshift deletion in the DPP region of the DSPP gene.

Clinical relevance

A DSPP mutation can alter the characteristics of the affected teeth, including tooth structure, hardness, mineral content, and ultrastructure.

Nur mit Berechtigung zugänglich

Shields ED, Bixler D, El-Kafrawy AM (1973) A proposed classification for heritable human dentine defects with a description of a new entity. Arch Oral Biol 18(4):543–IN7. https://doi.org/10.1016/0003-9969(73)90075-7CrossRefPubMed

Xiao S, Yu C, Chou X, Yuan W, Wang Y, Bu L, Fu G, Qian M, Yang J, Shi Y, Hu L (2001) Dentinogenesis imperfecta 1 with or without progressive hearing loss is associated with distinct mutations in DSPP. Nature gen 27(2):201–204CrossRef

Zhang X, Zhao J, Li C, Gao S, Qiu C, Liu P, Wu G, Qiang B, Lo WH, Shen Y (2001) DSPP mutation in dentinogenesis imperfecta Shields type II. Nature gen 27:151–152. https://doi.org/10.1038/84765CrossRef

DA MK, Suzanne Hart P, Hart TC, Hartsfield JK, Wilson A, Wright JT, Fisher LW (2008) A comprehensive analysis of normal variation and disease-causing mutations in the human DSPP gene. Hum Mutat 29(12):1392–1404. https://doi.org/10.1002/humu.20783CrossRef

Rajpar MH, Koch MJ, Davies RM, Mellody KT, Kielty CM, Dixon MJ (2002) Mutation of the signal peptide region of the bicistronic gene DSPP affects translocation to the endoplasmic reticulum and results in defective dentine biomineralization. Hum Mol Genet 11(21):2559–2565. https://doi.org/10.1093/hmg/11.21.2559CrossRefPubMed

de La Dure-Molla M, Philippe Fournier B, Berdal A (2015) Isolated dentinogenesis imperfecta and dentin dysplasia: revision of the classification. Eur J Hum Gen 23(4):445–451. https://doi.org/10.1038/ejhg.2014.159CrossRef

Sun Y, Lu Y, Chen S, Prasad M, Wang X, Zhu Q, Zhang J, Ball H, Feng J, Butler WT, Qin C (2010) Key proteolytic cleavage site and full-length form of DSPP. J Dent Res 89(5):498–503. https://doi.org/10.1177/0022034510363109CrossRefPubMedPubMedCentral

Li F, Liu Y, Liu H, Yang J, Zhang F, Feng H (2017) Phenotype and genotype analyses in seven families with dentinogenesis imperfecta or dentin dysplasia. Oral dis 23(3):360–366. https://doi.org/10.1111/odi.12621CrossRefPubMed

DA MK, Simmer JP, Hart PS, Hart TC, Fisher LW (2008) Overlapping DSPP mutations cause dentin dysplasia and dentinogenesis imperfecta. J Dent Res 87(12):1108–1111. https://doi.org/10.1177/154405910808701217CrossRef

10.

Song YL, Wang CN, Fan MW, Su B, Bian Z (2008) Dentin phosphoprotein frameshift mutations in hereditary dentin disorders and their variation patterns in normal human population. J Med Genet 45(7):457–464. https://doi.org/10.1136/jmg.2007.056911CrossRefPubMed

11.

Du Q, Cao L, Liu Y, Pang C, Wu S, Zheng L, Jiang W, Na X, Yu J, Wang S, Zhu X (2021) Phenotype and molecular characterizations of a family with dentinogenesis imperfecta shields type II with a novel DSPP mutation. Ann Transl Med 9:22. https://doi.org/10.21037/atm-21-5369CrossRef

12.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–423. https://doi.org/10.1038/gim.2015.30CrossRefPubMedPubMedCentral

13.

Turkkahraman H, Galindo F, Tulu US, Helms JA (2020) A novel hypothesis based on clinical, radiological, and histological data to explain the dentinogenesis imperfecta type II phenotype. Connect Tissue Res 61(6):526–536. https://doi.org/10.1080/03008207.2019.1631296CrossRefPubMed

14.

von Marschall Z, Fisher LW (2010) Dentin sialophosphoprotein (DSPP) is cleaved into its two natural dentin matrix products by three isoforms of bone morphogenetic protein-1 (BMP1). Matrix Biol 29(4):295–303. https://doi.org/10.1016/j.matbio.2010.01.002CrossRef

15.

Suzuki S, Sreenath T, Haruyama N, Honeycutt C, Terse A, Cho A, Kohler T, Müller R, Goldberg M, Kulkarni AB (2009) Dentin sialoprotein and dentin phosphoprotein have distinct roles in dentin mineralization. Matrix Biol: journal of the International Society for Matrix Biology. 28(4):221–229. https://doi.org/10.1016/j.matbio.2009.03.006CrossRef

16.

Ritchie H (2018) The functional significance of dentin sialoprotein-phosphophoryn and dentin sialoprotein. Int J Oral Sci 10(4):1–6. https://doi.org/10.1038/s41368-018-0035-9CrossRef

17.

Veis A, Perry A (1967) The phosphoprotein of the dentin matrix. Biochem 6(8):2409–2416. https://doi.org/10.1021/bi00860a017CrossRef

18.

Macdougall M, Zeichner-David M, Slavkin HC (1985) Production and characterization of antibodies against murine dentine phosphoprotein. Biochem J 232(2):493–500. https://doi.org/10.1042/bj2320493CrossRefPubMedPubMedCentral

19.

Weinstock M, Leblond C (1973) Radioautographic visualization of the deposition of a phosphoprotein at the mineralization front in the dentin of the rat incisor. J Cell Biol 56(3):838. https://doi.org/10.1083/jcb.56.3.838CrossRefPubMedPubMedCentral

20.

Rabie A, Veis A (1995) An immunocytochemical study of the routes of secretion of collagen and phosphophoryn from odontoblasts into dentin. Connect Tissue Res. 31(3):197–209. https://doi.org/10.3109/03008209509010811CrossRefPubMed

21.

Zanetti M, De Bernard B, Jontell M, Linde A (1981) Ca2+-binding studies of the phosphoprotein from rat-incisor dentine. Eur J Biochem 113(3):541–545. https://doi.org/10.1111/j.1432-1033.1981.tb05096.xCrossRefPubMed

22.

Marsh ME (1989) Binding of calcium and phosphate ions to dentin phosphophoryn. Biochem 28(1):346–352. https://doi.org/10.1021/bi00427a047CrossRef

23.

Stetler-Stevenson W, Veis A (1986) Type I collagen shows a specific binding affinity for bovine dentin phosphophoryn. Calcif Tissue Int 38(3):135–141. https://doi.org/10.1007/BF02556873CrossRefPubMed

24.

Prasad M, Butler WT, Qin C (2010) Dentin sialophosphoprotein in biomineralization. Connect Tissue Res 51(5):404–417. https://doi.org/10.3109/03008200903329789CrossRefPubMedPubMedCentral

25.

Yamakoshi Y, Lu Y, Hu JC, Kim JW, Iwata T, Kobayashi K, Nagano T, Yamakoshi F, Hu Y, Fukae M, Simmer JP (2008) Porcine dentin sialophosphoprotein: length polymorphisms, glycosylation, phosphorylation, and stability. J Biol Chem 283(21):14835–14844. https://doi.org/10.1074/jbc.M800633200CrossRefPubMedPubMedCentral

26.

Yang J, Kawasaki K, Lee M, Reid BM, Nunez SM, Choi M, Seymen F, Koruyucu M, Kasimoglu Y, Estrella‐Yuson N, Lin BP (2016) The dentin phosphoprotein repeat region and inherited defects of dentin. Mol Genet Genomic Med 4(1):28–38. https://doi.org/10.1002/mgg3.176CrossRefPubMed

27.

Wang SK, Chan HC, Makovey I, Simmer JP, Hu JC (2012) Novel PAX9 and COL1A2 missense mutations causing tooth agenesis and OI/DGI without skeletal abnormalities. PLoS One 7(12):e51533. https://doi.org/10.1371/journal.pone.0051533CrossRefPubMedPubMedCentral

28.

Almal SH, Padh H (2012) Implications of gene copy-number variation in health and diseases. Journal of human genetics. 57(1):6–13. https://doi.org/10.1038/jhg.2011.108CrossRefPubMed

29.

Lee JW, Hong J, Seymen F, Kim YJ, Kang J, Koruyucu M, Tuloglu N, Bayrak S, Song JS, Shin TJ, Hyun HK (2019) Novel frameshift mutations in DSPP cause dentin dysplasia type II. Oral dis 25(8):2044–2046. https://doi.org/10.1111/odi.13182CrossRefPubMedPubMedCentral

30.

Simmer JP, Zhang H, Moon SJ, Donnelly LA, Lee YL, Seymen F, Koruyucu M, Chan HC, Lee KY, Wu S, Hsiang CL (2022) The modified Shields classification and 12 families with defined DSPP mutations. Genes 13(5):858. https://doi.org/10.3390/genes13050858CrossRefPubMedPubMedCentral

31.

Taleb K, Lauridsen E, Daugaard‐Jensen J, Nieminen P, Kreiborg S (2018) Dentinogenesis imperfecta type II- genotype and phenotype analyses in three Danish families. Mol Genet Genomic Med 6(3):339–349. https://doi.org/10.1002/mgg3.375CrossRefPubMedPubMedCentral

32.

Park H, Hyun HK, Woo KM, Kim JW (2020) Physicochemical properties of dentinogenesis imperfecta with a known DSPP mutation. Arch Oral Biol 117:104815. https://doi.org/10.1016/j.archoralbio.2020.104815CrossRefPubMed

33.

Lee SK, Lee KE, Hwang YH, Kida M, Tsutsumi T, Ariga T, Park JC, Kim JW (2011) Identification of the DSPP mutation in a new kindred and phenotype–genotype correlation. Oral Dis 17(3):314–319. https://doi.org/10.1111/j.1601-0825.2010.01760.xCrossRefPubMed

34.

Wieczorek A, Loster J (2013) Dentinogenesis imperfecta type II: ultrastructure of teeth in sagittal sections. Folia Histochem Cytobiol 51(3):244–247. https://doi.org/10.5603/fhc.2013.0035CrossRefPubMed

35.

Nutchoey O, Intarak N, Theerapanon T, Thaweesapphithak S, Boonprakong L, Srijunbarl A, Porntaveetus T, Shotelersuk V (2021) Phenotypic features of dentinogenesis imperfecta associated with osteogenesis imperfecta and COL1A2 mutations. Oral Surg Oral Med Oral Radiol 131(6):694–701. https://doi.org/10.1016/j.oooo.2021.01.003CrossRef

36.

Kerebel B, Daculsi G, Menanteau J, Kerebel LM (1981) The inorganic phase in dentinogenesis imperfecta. J of dental res 60(9):1655–1660. https://doi.org/10.1177/00220345810600090401CrossRef

37.

Sabel N, Norén JG, Robertson A, Cornell DH (2020) X-ray microanalysis of dentine in primary teeth diagnosed dentinogenesis imperfecta type II. Eur Arch Paediatr Dent 21(4):527–535. https://doi.org/10.1007/s40368-018-0392-2CrossRefPubMed

38.

Castiglioni S, Cazzaniga A, Albisetti W, Maier JA Magnesium and osteoporosis: current state of knowledge and future research directions. Nutrients 31(5):3022–3033. https://doi.org/10.3390/nu5083022

39.

Wiesmann HP, Höhling HJ, Zierold K, Barckhaus R (1995) Elemental distributions in predentine associated with dentine mineralization in rat incisor. Connect Tissue Res 33(1-3):179–184. https://doi.org/10.3390/nu5083022CrossRefPubMed

40.

Intarak N, Budsamongkol T, Theerapanon T, Chanamuangkon T, Srijunbarl A, Boonprakong L, Porntaveetus T, Shotelersuk V (2021) Tooth ultrastructure of a novel COL1A2 mutation expanding its genotypic and phenotypic spectra. Oral dis 27(5):1257–1267. https://doi.org/10.1111/odi.13657CrossRefPubMed

41.

Chen S, Rani S, Wu Y, Unterbrink A, Gu TT, Gluhak-Heinrich J, Chuang HH, MacDougall M (2005) Differential regulation of dentin sialophosphoprotein expression by Runx2 during odontoblast cytodifferentiation. J Biol Chem. 280(33):29717–29727. https://doi.org/10.1074/jbc.M502929200CrossRefPubMed

42.

Seow W (2003) Diagnosis and management of unusual dental abscesses in children. Aust Dent J 48(3):156–168. https://doi.org/10.1111/j.1834-7819.2003.tb00026.xCrossRefPubMed

43.

Porntaveetus T, Osathanon T, Nowwarote N, Pavasant P, Srichomthong C, Suphapeetiporn K, Shotelersuk V (2018) Dental properties, ultrastructure, and pulp cells associated with a novel DSPP mutation. Oral diseases. 24(4):619–627. https://doi.org/10.1111/odi.12801CrossRefPubMed

Titel: Identification of DSPP novel variants and phenotype analysis in dentinogenesis dysplasia Shields type II patients
verfasst von: Qin Du
Li Cao
Nana Yan
Sujun Kang
Mu Lin
Peilin Cao
Ran Jia
Chenyang Wang
Hanyu Qi
Yue Yu
Jing Zou
Jiyun Yang
Publikationsdatum: 05.04.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Clinical Oral Investigations / Ausgabe 7/2023
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-023-05009-y

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Identification of DSPP novel variants and phenotype analysis in dentinogenesis dysplasia Shields type II patients