Whole exome sequencing identifies an AMBN missense mutation causing severe autosomal-dominant amelogenesis imperfecta and dentin disorders

Abstract

A mutation on a gene involved in healthy tooth development may cause both enamel and dentin disorders. The ameloblastin enamel protein, and its associated gene, AMBN, play vital roles in enamel formation and tooth remodelling. Mutations on AMBN can cause amelogenesis imperfecta (AI), a genetic and hereditory condition resulting in enamel defects and severe tooth decay. Now, Fu Xiong and Bu-Ling Wu at Southern Medical University in Guangzhou, China, and co-workers have identified an AMBN mutation found in both enamel and dentin defect disorders. The researchers analyzed extracted teeth from a Chinese patient with both AI and a severe dentin disorder, along with teeth from affected and non-affected members of the same family, and compared the results with a control group. They identified a rare mutation on AMBN common to all affected individuals.

References

[1] Smith CE. Cellular and chemical events during enamel maturation. Crit. Rev. Oral. Biol. Med., 1998, 9: 128-161.

[2] Simmer JP, Fincham AG. Molecular mechanisms of dental enamel formation. Crit. Rev. Oral. Biol. Med., 1995, 6: 84-108.

[3] Damsky CH, Werb Z. Signal transduction by integrin receptors for extracellular matrix: cooperative processing of extracellular information. Curr. Opin. Cell. Biol., 1992, 4: 772-781.

[4] Lin CQ, Bissell MJ. Multi-faceted regulation of cell differentiation by extracellular matrix. FASEB J., 1993, 7: 737-743.

[5] Černý R, Slaby I, Hammarström L, Wurtz T. A novel gene expressed in rat ameloblasts codes for proteins with cell binding domains. J. Bone Miner. Res., 1996, 11: 883-891.

[6] Uchida T, . Sheath proteins: synthesis, secretion, degradation and fate in forming enamel. Eur. J. Oral. Sci., 1998, 106: 308-314.

[7] Rajpar MH, Harley K, Laing C, Davies RM, Dixon MJ. Mutation of the gene encoding the enamel-specific protein, enamelin, causes autosomal-dominant amelogenesis imperfecta. Hum. Mol. Genet., 2001, 10: 1673-1677.

[8] Poulter JA, . Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta. Hum. Mol. Genet., 2014, 23: 5317-5324.

[9] Witkop, C. J. & Sauk, J. J. Heritable Defects of Enamel. The C.V. Mosby Company,Maryland Heights,MN,USA,151–226 (1976).

[10] Backman B, Holm AK. Amelogenesis imperfecta: prevalence and incidence in a northern Swedish county. Community Dent. Oral. Epidemiol., 1986, 14: 43-47.

[11] Lagerström M, . A deletion in the amelogenin gene (AMG) causes X-linked amelogenesis imperfecta (AIH1). Genomics, 1991, 10: 971-975.

[12] Hart PS, . Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. J. Med. Genet., 2004, 41: 545-549.

[13] Kim JW, . MMP-20 mutation in autosomal recessive pigmented hypomaturation amelogenesis imperfecta. J. Med. Genet., 2005, 42: 271-275.

[14] O'Sullivan J, . Whole-exome sequencing identifies FAM20A mutations as a cause of amelogenesis imperfecta and gingival hyperplasia syndrome. Am. J. Hum. Genet., 2011, 88: 616-620.

[15] Parry DA, . Mutations in C4orf26, encoding a peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta. Am. J. Hum. Genet., 2012, 91: 565-571.

[16] Smith CEL, . Deletion of amelotin exons 3–6 is associated with amelogenesis imperfecta. Hum. Mol. Genet., 2016, 25: 3578-3587.

[17] Parry DA, . Identification of mutations in SLC24A4, encoding a potassium-dependent sodium/calcium exchanger, as a cause of amelogenesis imperfecta. Am. J. Hum. Genet., 2013, 92: 307-312.

[18] Smith CEL, . Amelogenesis imperfecta; genes, proteins, and pathways. Front. Physiol., 2017, 8: 435.

[19] Parry DA, . Mutations in the pH-sensing G-protein-coupled receptor GPR68 cause amelogenesis imperfecta. Am. J. Hum. Genet., 2016, 99: 984-990.

[20] Kim JW, . LAMB3 mutations causing autosomal-dominant amelogenesis imperfecta. J. Dent. Res., 2013, 92: 899-904.

[21] Poulter JA, . Whole-exome sequencing, without prior linkage, identifies a mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta. Eur. J. Hum. Genet., 2014, 22: 132-135.

[22] Wang SK, . ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis imperfecta. Hum. Mol. Genet., 2014, 23: 2157-2163.

[23] Poulter JA, . A missense mutation in ITGB6 causes pitted hypomineralized amelogenesis imperfecta. Hum. Mol. Genet., 2014, 23: 2189-2197.

[24] McGrath JA, . Compound heterozygosity for a dominant glycine substitution and a recessive internal duplication mutation in the type XVII collagen gene results in junctional epidermolysis bullosa and abnormal dentition. Am. J. Pathol., 1996, 148: 1787-1796.

[25] Yuen W, Pasmooij A, Stellingsma C, Jonkman M. Enamel defects in carriers of a novel LAMA3 mutation underlying epidermolysis bullosa. Acta Derm. Venereol., 2012, 92: 695-696.

[26] Kim JW, . FAM83H mutations in families with autosomal-dominant hypocalcified amelogenesis imperfecta. Am. J. Hum. Genet., 2008, 82: 489-494.

[27] El-Sayed W, . Mutations in the beta propeller WDR72 cause autosomal-recessive hypomaturation amelogenesis imperfecta. Am. J. Hum. Genet., 2009, 85: 699-705.

[28] Smith CEL, . Defects in the acid phosphatase ACPT cause recessive hypoplastic amelogenesis imperfecta. Eur. J. Hum. Genet., 2017, 25: 1015-1019.

[29] Seymen F, . Recessive mutations in ACPT, encoding testicular acid phosphatase, cause hypoplastic amelogenesis imperfecta. Am. J. Hum. Genet., 2016, 99: 1199-1205.

[30] Wang SK, . Enamel malformations associated with a defined dentin sialophosphoprotein mutation in two families. Eur. J. Oral. Sci., 2011, 119: 158-167.

[31] Kim YJ, . Unexpected identification of a recurrent mutation in the DLX3 gene causing amelogenesis imperfecta. Oral. Dis., 2016, 22: 297-302.

[32] Smith CE, . Consequences for enamel development and mineralization resulting from loss of function of ameloblastin or enamelin. Eur. J. Oral. Sci., 2009, 117: 485-497.

[33] Paine ML, Wang HJ, Luo W, Krebsbach PH, Snead ML. A transgenic animal model resembling amelogenesis imperfecta related to ameloblastin overexpression. J. Biol. Chem., 2003, 278: 19447-19452.

[34] Prasad MK, . A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement. J. Med. Genet., 2016, 53: 98-110.

[35] Nanci, A. & Cate, A. R. T. Dentin-Pulp Complex. In: Ten Cate's Oral Histology: Development,Structure and Function.7th edn,Mosby Elsevier,Maryland Heights,MN,USA,191–238 (2008).

[36] Arana-Chavez VE, Massa LF. Odontoblasts: the cells forming and maintaining dentine. Int. J. Biochem. Cell Biol., 2004, 36: 1367-1373.

[37] Fong CD, Černý R, Hammarström L, Slaby I. Sequential expression of an amelin gene in mesenchymal and epithelial cells during odontogenesis in rats. Eur. J. Oral. Sci., 1998, 106: 324-330.

[38] Barron MJ, McDonnell ST, MacKie I, Dixon MJ. Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia. Orphanet J. Rare Dis., 2008, 3

[39] De La Dure-Molla M, Philippe FB, Berdal A. Isolated dentinogenesis imperfecta and dentin dysplasia: revision of the classification. Eur. J. Hum. Genet., 2015, 23: 445-451.

[40] Duan X, . Mutations in COL1A1 gene change dentin nanostructure. Anat. Rec. (Hoboken), 2016, 299: 511-519.

[41] Martin E, Shapiro JR. Osteogenesis imperfecta: epidemiology and pathophysiology. Curr. Osteoporos. Rep., 2007, 5: 91-97.

[42] Porntaveetus T, . Dental properties, ultrastructure, and pulp cells associated with a novel DSPP mutation. Oral. Dis., 2018, 24: 619-627.

[43] McKnight DA, . A comprehensive analysis of normal variation and disease-causing mutations in the human DSPP gene. Hum. Mutat., 2008, 29: 1392-1404.

[44] Rajpar MH, . 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., 2002, 11: 2559-2565.

[45] Song Y, . Phenotypes and genotypes in 2 DGI families with different DSPP mutations. Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. Endod., 2006, 102: 360-374.

[46] Bloch-Zupan A, . Homozygosity mapping and candidate prioritization identify mutations, missed by whole-exome sequencing, in SMOC2, causing major dental developmental defects. Am. J. Hum. Genet., 2011, 89: 773-781.

[47] Cherkaoui JI, . Inhabitual autosomal recessive form of dentin dysplasia type I in a large consanguineous Moroccan family. Eur. J. Med. Genet., 2013, 56: 442-444.

[48] Yang Q, . A splicing mutation in VPS4B causes dentin dysplasia I. J. Med. Genet., 2016, 53: 624-633.

[49] Xiong F, . Mutation in SSUH2 causes autosomal-dominant dentin dysplasia type I. Hum. Mutat., 2017, 38: 95-104.

[50] Nakamura Y, . Ameloblastin fusion protein enhances pulpal healing and dentin formation in porcine teeth. Calcif. Tissue Int., 2006, 78: 278-284.

[51] Shahmoradi M, Swain MV. Quantitative characterization and micro-CT mineral mapping of natural fissural enamel lesions. J. Dent., 2016, 46: 23-29.

[52] Huang TTY, Jones AS, He LH, Darendeliler MA, Swain MV. Characterisation of enamel white spot lesions using X-ray micro-tomography. J. Dent., 2007, 35: 737-743.

[53] Dowker SEP, Elliott JC, Davis GR, Wilson RM, Cloetens P. Synchrotron x-ray microtomographic investigation of mineral concentrations at micrometre scale in sound and carious enamel. Caries Res., 2004, 38: 514-522.

[54] Dowker SEP, Elliott JC, Davis GR, Wilson RM, Cloetens P. Three-dimensional study of human dental fissure enamel by synchrotron X-ray microtomography. Eur. J. Oral. Sci., 2006, 114: 353-359.

[55] Weatherell JA, Weidmann SM, Hamm SM. Density patterns in enamel. Caries Res., 1967, 1: 42-51.

[56] Delsuc F, Gasse B, Sire JY. Evolutionary analysis of selective constraints identifies ameloblastin (AMBN) as a potential candidate for amelogenesis imperfecta. BMC Evol. Biol., 2015, 15: 148.

[57] Kawasaki K, Weiss KM. SCPP gene evolution and the dental mineralization continuum. J. Dent. Res., 2008, 87: 520-531.

[58] Silvent J, Sire JY, Delgado S. The dentin matrix acidic phosphoprotein 1 (DMP1) in the light of mammalian evolution. J. Mol. Evol., 2013, 76: 59-70.

[59] Morkmued S, . Retinoic acid excess impairs amelogenesis inducing enamel defects. Front. Physiol., 2016, 7: 673.

[60] Wald T, . Intrinsically disordered proteins drive enamel formation via an evolutionarily conserved self-assembly motif. Proc. Natl Acad. Sci. USA, 2017, 114: E1641-E1650.

[61] Iwata T, . Processing of ameloblastin by MMP-20. J. Dent. Res., 2007, 86: 153-157.

[62] Zhang Y, Zhang X, Lu X, Atsawasuwan P, Luan X. Ameloblastin regulates cell attachment and proliferation through RhoA and p27. Eur. J. Oral. Sci., 2011, 119: 280-285.

[63] Malmgren B, Lindskog S, Elgadi A, Norgren S. Clinical, histopathologic, and genetic investigation in two large families with dentinogenesis imperfecta type II. Hum. Genet., 2004, 114: 491-498.

[64] Atsawasuwan P, . Ameloblastin inhibits cranial suture closure by modulating Msx2 expression and proliferation. PLoS ONE, 2013, 8: e52800.

[65] Chun YHP, . Transgenic rescue of enamel phenotype in Ambn null mice. J. Dent. Res., 2010, 89: 1414-1420.

[66] Qu Q, Haitina T, Zhu M, Ahlberg PE. New genomic and fossil data illuminate the origin of enamel. Nature, 2015, 526: 108-111.

[67] Jernvall J, Thesleff I. Reiterative signaling and patterning during mammalian tooth morphogenesis. Mech. Dev., 2000, 92: 19-29.

[68] Verdelis K, . Accelerated enamel mineralization in Dspp mutant mice. Matrix Biol., 2016, 52-54: 246-259.

[69] Dhamija S, Krebsbach PH. Role of Cbfa1 in ameloblastin gene transcription. J. Biol. Chem., 2001, 276: 35159-35164.

[70] Camilleri S, McDonald F. Runx2 and dental development. Eur. J. Oral. Sci., 2006, 114: 361-373.

[71] Yang F, . A feedback loop between RUNX2 and the E3 ligase SMURF1 in regulation of differentiation of human dental pulp stem cells. J. Endod., 2014, 40: 1579-1586.

[72] Zhang C, Chang J, Sonoyama W, Shi S, Wang CY. Inhibition of human dental pulp stem cell differentiation by notch signaling. J. Dent. Res., 2008, 87: 250-255.

[73] Chen Y, Zhang Y, Ramachandran A, George A. DSPP is essential for normal development of the dental-craniofacial complex. J. Dent. Res., 2016, 95: 302-310.

[74] Spahr A, . Expression of amelin and trauma-induced dentin formation. Clin. Oral. Investig., 2002, 6: 51-57.

[75] Wright T. Amelogenesis imperfecta. Eur. J. Oral. Sci., 2011, 119: 338-341.

[76] Crawford PJM, Aldred M, Bloch-Zupan A. Amelogenesis imperfecta. Orphanet J. Rare Dis., 2007, 2: 1-11.

[77] Ma P, . The importance of serine phosphorylation of ameloblastin on enamel formation. J. Dent. Res., 2016, 95: 1408-1414.

[78] Hu JCC, Yamakoshi Y. Enamelin and autosomal-dominant amelogenesis imperfecta. Crit. Rev. Oral. Biol. Med., 2003, 14: 387-398.