Versiones
- 2024-07-12 (2)
- 2021-09-30 (1)
Palabras clave
amelogénesis imperfecta
hipoplasia
esmalte
hipoplasia
esmalte
Cómo citar
Mecanismos moleculares de la amelogénesis imperfecta. Una revisión de los genes ENAM, AMBN, FAM83H, MMP20 y KLK4. (2021). Odontoestomatología, 23(38). https://doi.org/10.22592/1688-9339-ode-23-38-e306
Resumen
La amelogénesis imperfecta (AI) es un trastorno hereditario que afecta la estructura y apariencia clínica del esmalte dental. Hasta la fecha, se han asociado las mutaciones de 18 genes como la etiología de la AI no sindrómica. El objetivo de este trabajo es actualizar los conocimientos vigentes acerca de los genes ENAM, AMBN, FAM83H, MMP20 yKLK4causantes de los diferentes tipos de AI.
Metodología: Se realizó una búsqueda bibliográfica considerando artículos científicos desde el 2003 al 2021 sobre mutaciones en los genes mencionados en los siguientes portales: scielo, Pubmed/MEDLINE, Cochrane y Springer Link.
Resultados: 37 artículos cumplieron los criterios de inclusión y fueron utilizados para esta revisión.
Conclusiones: Dependiendo del gen implicado, las alteraciones del esmalte pueden mostrar una variedad de características. Los mecanismos biológicos que conducen a la enfermedad son múltiples y variados, sin embargo, muchos de ellos no están del todo claro aún,
por lo que se requerirá de más investigaciones para mejorar nuestra comprensión del tema.
Referencias
1. Sapp J.P; Eversole L.R; Wysocki G.P. Patología oral y maxilofacial contemporánea, 2º edición. Madrid: Elsevier, 2005: 14-16.
2. Witkop C.J. Jr. Amelogenesis imperfecta, dentinogenesisimperfecta and dentin dysplasia revisited: problems in classification. J. Oral. Pathol. 1988; 17(9-10): 547-553.
3. Crawford P.J; Aldred M; Bloch-Zupan A. Amelogenesis imperfecta. Orphanet J. Rare. Dis. 2007; 2: 17.
4. Hu J.C; Chun Y.H; Al Hazzazzi T; Simmer J.P. Enamel formation and amelogenesis imperfecta. Cellstissuesorgans. 2007; 186(1): 78-85.
5. Aldred M.J; Crawford P.J.M; Savarirayan R. Amelogenesis imperfecta: a classification and catalogue for the 21st century. Oral. Dis. 2003; 9(1): 19-23.
6. Prasad M.K; Laouina S; El Alloussi M; Dollfus H; Bloch-Zupan A. Amelogenesis imperfecta: 1 family, 2 phenotypes, and 2 mutated genes. J. Dent. Res. 2016; 95(13): 1457-1463.
7. Smith C.E.L; Poulter J.A; Antanaviciute A; Kirkham J; Brookes S.J; Inglehearn C.F; Mighell A.J. Amelogenesis Imperfecta; Genes, Proteins, and Pathways. Front. Physiol. 2017; 8: 435.
8. Kim J.W; Simmer J.P; Lin B.P.L; Seymen F; Bartlett J.D; Hu J.C.C. Mutational analysis of candidate
genes in 24 amelogenesis imperfecta families. Eur. J. Oral. Sci. 2006; 114(suppl1): 3-12.
9. Simancas-Escorcia V; Natera A; Acosta de Camargo M.G. Genes involved in amelogenesis imperfecta. Part I. Rev. Fac. Odontol. Univ. Antioq. 2018; 30(1): 105-120.
10. Lee S.K; Lee K.E; Jeong T.S; Hwang Y.H; Kim S; Hu J.C.C; Simmer J.P; Kim J.W. FAM83H mutations cause ADHCAI and alter intracellular protein localization. J. Dent. Res. 2011; 90(3): 377-381.
11. Kim J.W; Lee S.K; Lee Z.H; Park J.C; Lee K.E; Lee M.H. FAM83H mutations in families with autosomal-dominant hypocalcified amelogenesis imperfecta. Am. J. Hum. Genet. 2008; 82(2): 489-494.
12. Zhang H; Hu Y; Seymen F; Koruyucu M; Kasimoglu Y; Wang S.K; Wright J.T; Havel M.W; Zhang C; Kim J.W; Simmer J.P; Hu J.C.C. ENAM mutations and Digenic Inheritance. Mol. Genet. Genomic Med. 2019; 7(10): e928.
13. Koruyucu M; Kang J; Kim Y.J; Seymen F; Kasimoglu Y; Lee Z.H; Shin T.J; Hyun H.K; Kim Y.J; Lee S.H; Hu J.C.C; Simmer J.P; Kim J.W. Hypoplastic AI with highly variable expressivity caused by ENAM mutations. J. Dent. Res. 2018; 97(9): 1064-1069.
14. Seymen F; Lee K.E; Koruyucu M; Gencay K; Bayram M; Tuna E.B; Lee Z.H; Kim J.W. ENAM mutations with Incomplete Penetrance. J. Dent. Res. 2014; 93(10): 988-992.
15. Wang X; Zhao Y; Yang Y; Qin M. Novel ENAM and LAMB3 mutations in chinese families with hypoplastic amelogenesis imperfecta. Plos One. 2015; 10(3): e0116514.
16. Hart T.C; Hart P.S; Gorry M.C; Michalec M.D; Ryu O.H; Uygur C; Ozdemir D; Firatli S; Aren G; Firatli E. Novel ENAM mutation responsible for autosomal recessive amelogenesis imperfecta and localised enamel defects. J. Med. Genet. 2003; 40(12): 900-906.
17. Siddiqui S; Al-Jawad M. Enamelin directs crystallite organization at the enamel-dentine junction. J. Dent. Res. 2016; 95(5): 580-587.
18. Brookes S.J; Barron M.J; Smith C.E.L; Poulter J.A; Mighell A.J; Inglehearn C.F; Brown C.J; Rodd H; Kirkham J; Dixon M.J. Amelogenesis imperfecta caused by N-Terminal enamelin point mutations in mice and men is driven by endoplasmic reticulum stress. Hum. Mol. Genet. 2017; 26(10): 1863-1876.
19. Delsuc F; Gasse B; Sire J.Y. Evolutionary analysis of selective constraints identifies ameloblastin (AMBN) as a potential candidate for amelogenesis imperfecta. BMC Evolutionary Biology. 2015; 15: 148.
20. Poulter J.A; Murillo G; Brookes S.J; Smith C.E.L; Parry D.A; Silva S; Kirkham J; Inglehearn C.F; Mighell A.J. Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta. Hum. Mol. Genet. 2014; 23(20): 5317-5324.
21. Fukumoto S; Kiba T; Hall B; Iehara N; Nakamura T; Longenecker G; Krebsbach P.H; Nanci A; Kulkarni A.B; Yamada Y. Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts. J. Cell Biol. 2004; 167(5): 973-983.
22. Sire J.Y; Davit-Béal T; Delgado S; Gu X. The origin and evolution of enamel mineralization genes. Cells Tissues Organs. 2007; 186(1): 25-48.
23. Liang T; Hu Y; Smith C.E; Richardson A.S; Zhang H; Yang J; Lin B; Wang S.K; Kim J.W; Chun Y.H; Simmer J.P; Hu J.C.C. AMBN mutations causing hypoplastic amelogenesis imperfecta and Ambn knockout-NLS-laczknockin mice exhibiting failed amelogenesis and Ambn tissue-specificity. Mol. Genet. Genomic Med. 2019; 7(9): e929.
24. Lu T; Li M; Xu X; Xiong J; Huang C; Zhang X; Hu A; Peng L; Cai D; Zhang L; Wu B; Xiong F. Whole exome sequencing identifies an AMBN missense mutation causing severe autosomal-dominant amelogenesis imperfecta and dentin disorders. Int. J. Oral Sci. 2018; 10(3): 26.
25. Wang S.K; Zhang H; Hu C.Y; Liu J.F; Chadha S; Kim J.W; Simmer J.P; Hu J.C.C. FAM83H and autosomal dominant hypocalcified amelogenesis imperfecta. J. Dent. Res. 2021; 100(3): 293-301.
26. Urzua B; Martinez C; Ortega-Pinto A; Adorno D; Morales-Bozo I; Riadi G; Jara L; Plaza A; Lefimil C; Lozano C; Reyes M. Novel missense mutation of the FAM83H gene causes retention of amelogenin and a mild clinical phenotype of hypocalcified enamel. Arch. Oral Biol. 2015; 60(9): 1356-1367.
27. Wang S.K; Hu Y; Yang J; Smith C.E; Richardson A.S; Yamakoshi Y; Lee Y.L; Seymen F; Koruyucu M; Gencay K; Lee M; Choi M; Kim J.W; Hu J.C.C; Simmer J.P. Fam83h null mice support a neomorphic mechanism for human ADHCAI. Mol. Genet. Genomic Med. 2015; 4(1): 46-67.
28. Wang S.K; Hu Y; Smith C.E; Yang J; Zeng C; Kim J.W; Hu J.C.C; Simmer J.P. The enamel phenotype in homozygous Fam83h truncation mice. Mol. Genet. Genomic Med. 2019; 7(6): e724.
29. Zheng, Y; Lu T; Chen J; Li M; Xiong J; He F; Gan Z; Guo Y; Zhang L; Xiong F. The gain-of-function FAM83H mutation caused hypocalcification amelogenesis imperfecta in a chinese family. Clin. Oral Invest. 2021; 25(5): 2915-2923.
30. Xin W; Wenjun W; Man Q; Yuming Z. Novel FAM83H mutations in patients with amelogenesis imperfecta. Sci. Rep. 2017; 7(1): 6075.
31. Yu S; Quan J; Wang X; Sun X; Zhang X; Liu Y; Zhang C; Zheng S. A novel FAM83H mutation in one Chinese family with autosomal-dominant hypocalcification amelogenesis imperfecta. Mutagenesis. 2018; 33(4): 333-340.
32. Zhang C; Song Y; Bian Z; Ultrastructural analysis of the teeth affected with amelogenesis imperfecta resulting from FAM83H mutations and review of the literatures. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2015; 119(2): e69-76.
33. Kuga T; Sasaki M; Mikami T; Miake Y; Adachi J; Shimizu M; Saito Y; Koura M; Takeda Y; Matsuda J; Tomonaga T; Nakayama Y. FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes. Sci. Rep. 2016; 6: 26557.
34. Gasse B; Prasad M; Delgado S; Huckert M; Kawczynski M; Garret-Bernardin A; Lopez-Cazaux S; Bailleul-Forestier I; Manière M.C; Stoetzel C; Bloch-Zupan A; Sire J.Y. Evolutionary analysis predicts sensitive positions of MMP20 and validates newly-and previously-identified MMP20 mutations causing amelogenesis imperfecta. Front. Physiol. 2017; 8: 398.
35. Wang S.K; Zhang H; Chavez M.B; Hu Y; Seymen F; Koruyucu M; Kasimoglu Y; Colvin C.D; Kolli T.N; Tan M.H; Wang Y.L; Lu P.Y; Kim J.W; Foster B.L; Bartlett J.D; Simmer J.P; Hu J.C.C. Dental malformations associated with biallelic MMP20 mutations. Mol. Genet. Genomic Med. 2020; 8(8): e1307.
36. Seymen F; Park J.C; Lee K.E; Lee H.K; Lee D.S; Koruyucu M; Gencay K; Bayram M; Tuna E.B; Lee Z.H; Kim Y.J; Kim J.W. Novel MMP20 and KLK4 mutations in amelogenesis imperfecta. J. Dent. Res. 2015; 94(8): 1063-1069.
37. Kim Y.J; Kang J; Seymen F; Koruyucu M; Zhang H; Kasimoglu Y; Bayram M; Tuna-Ince E.B; Bayrak
S; Tuloglu N; Hu J.C.C; Simmer J.P; Kim J.W. Alteration of exon definition causes amelogenesis imperfecta. J. Dent. Res. 2020; 99(4): 410-418.
38. Kim Y.J; Kang J; Seymen F; Koruyucu M; Gencay K; Shin T.J; Hyun H.K; Lee Z.H; Hu J.C.C; Simmer J.P; Kim J.W. Analyses of MMP20 missense mutations in two families with hypomaturation amelogenesis imperfecta. Front. Physiol. 2017; 8: 229.
39. Hu Y; Smith C.E; Richardson A.S; Bartlett J.D; Hu J.C; Simmer J.P. MMP20, KLK4, and MMP20/KLK4 double null mice define roles for matrix proteases during dental enamel formation. Mol. Genet. Genomic Med. 2015; 4(2): 178-196.
40. Smith C.E.L; Kirkham J; Day P.F; Soldani F; mcderra E.J; Poulter J.A; Inglehearn C.F; Mighell A.J; Brookes S.J. A fourth KLK4 mutation is associated with enamel hypomineralisation and structural abnormalities. Front. Physiol. 2017; 8: 333.
41. Hart P.S; Hart T.C; Michalec M.D; Ryu, O.H; Simmons D; Hong S; Wright J.T. Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. J. Med. Genet. 2004; 41(7): 545-549.
42. Wang S.K; Hu Y; Simmer J.P; Seymen F; Estrella N.M.R.P; Pal S; Reid B.M; Yildirim M; Bayram M; Bartlett J.D; Hu J.C.C. Novel KLK4 and MMP20 mutations discovered by whole-exome sequencing. J. Dent. Res. 2013; 92(3): 266-271.
2. Witkop C.J. Jr. Amelogenesis imperfecta, dentinogenesisimperfecta and dentin dysplasia revisited: problems in classification. J. Oral. Pathol. 1988; 17(9-10): 547-553.
3. Crawford P.J; Aldred M; Bloch-Zupan A. Amelogenesis imperfecta. Orphanet J. Rare. Dis. 2007; 2: 17.
4. Hu J.C; Chun Y.H; Al Hazzazzi T; Simmer J.P. Enamel formation and amelogenesis imperfecta. Cellstissuesorgans. 2007; 186(1): 78-85.
5. Aldred M.J; Crawford P.J.M; Savarirayan R. Amelogenesis imperfecta: a classification and catalogue for the 21st century. Oral. Dis. 2003; 9(1): 19-23.
6. Prasad M.K; Laouina S; El Alloussi M; Dollfus H; Bloch-Zupan A. Amelogenesis imperfecta: 1 family, 2 phenotypes, and 2 mutated genes. J. Dent. Res. 2016; 95(13): 1457-1463.
7. Smith C.E.L; Poulter J.A; Antanaviciute A; Kirkham J; Brookes S.J; Inglehearn C.F; Mighell A.J. Amelogenesis Imperfecta; Genes, Proteins, and Pathways. Front. Physiol. 2017; 8: 435.
8. Kim J.W; Simmer J.P; Lin B.P.L; Seymen F; Bartlett J.D; Hu J.C.C. Mutational analysis of candidate
genes in 24 amelogenesis imperfecta families. Eur. J. Oral. Sci. 2006; 114(suppl1): 3-12.
9. Simancas-Escorcia V; Natera A; Acosta de Camargo M.G. Genes involved in amelogenesis imperfecta. Part I. Rev. Fac. Odontol. Univ. Antioq. 2018; 30(1): 105-120.
10. Lee S.K; Lee K.E; Jeong T.S; Hwang Y.H; Kim S; Hu J.C.C; Simmer J.P; Kim J.W. FAM83H mutations cause ADHCAI and alter intracellular protein localization. J. Dent. Res. 2011; 90(3): 377-381.
11. Kim J.W; Lee S.K; Lee Z.H; Park J.C; Lee K.E; Lee M.H. FAM83H mutations in families with autosomal-dominant hypocalcified amelogenesis imperfecta. Am. J. Hum. Genet. 2008; 82(2): 489-494.
12. Zhang H; Hu Y; Seymen F; Koruyucu M; Kasimoglu Y; Wang S.K; Wright J.T; Havel M.W; Zhang C; Kim J.W; Simmer J.P; Hu J.C.C. ENAM mutations and Digenic Inheritance. Mol. Genet. Genomic Med. 2019; 7(10): e928.
13. Koruyucu M; Kang J; Kim Y.J; Seymen F; Kasimoglu Y; Lee Z.H; Shin T.J; Hyun H.K; Kim Y.J; Lee S.H; Hu J.C.C; Simmer J.P; Kim J.W. Hypoplastic AI with highly variable expressivity caused by ENAM mutations. J. Dent. Res. 2018; 97(9): 1064-1069.
14. Seymen F; Lee K.E; Koruyucu M; Gencay K; Bayram M; Tuna E.B; Lee Z.H; Kim J.W. ENAM mutations with Incomplete Penetrance. J. Dent. Res. 2014; 93(10): 988-992.
15. Wang X; Zhao Y; Yang Y; Qin M. Novel ENAM and LAMB3 mutations in chinese families with hypoplastic amelogenesis imperfecta. Plos One. 2015; 10(3): e0116514.
16. Hart T.C; Hart P.S; Gorry M.C; Michalec M.D; Ryu O.H; Uygur C; Ozdemir D; Firatli S; Aren G; Firatli E. Novel ENAM mutation responsible for autosomal recessive amelogenesis imperfecta and localised enamel defects. J. Med. Genet. 2003; 40(12): 900-906.
17. Siddiqui S; Al-Jawad M. Enamelin directs crystallite organization at the enamel-dentine junction. J. Dent. Res. 2016; 95(5): 580-587.
18. Brookes S.J; Barron M.J; Smith C.E.L; Poulter J.A; Mighell A.J; Inglehearn C.F; Brown C.J; Rodd H; Kirkham J; Dixon M.J. Amelogenesis imperfecta caused by N-Terminal enamelin point mutations in mice and men is driven by endoplasmic reticulum stress. Hum. Mol. Genet. 2017; 26(10): 1863-1876.
19. Delsuc F; Gasse B; Sire J.Y. Evolutionary analysis of selective constraints identifies ameloblastin (AMBN) as a potential candidate for amelogenesis imperfecta. BMC Evolutionary Biology. 2015; 15: 148.
20. Poulter J.A; Murillo G; Brookes S.J; Smith C.E.L; Parry D.A; Silva S; Kirkham J; Inglehearn C.F; Mighell A.J. Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta. Hum. Mol. Genet. 2014; 23(20): 5317-5324.
21. Fukumoto S; Kiba T; Hall B; Iehara N; Nakamura T; Longenecker G; Krebsbach P.H; Nanci A; Kulkarni A.B; Yamada Y. Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts. J. Cell Biol. 2004; 167(5): 973-983.
22. Sire J.Y; Davit-Béal T; Delgado S; Gu X. The origin and evolution of enamel mineralization genes. Cells Tissues Organs. 2007; 186(1): 25-48.
23. Liang T; Hu Y; Smith C.E; Richardson A.S; Zhang H; Yang J; Lin B; Wang S.K; Kim J.W; Chun Y.H; Simmer J.P; Hu J.C.C. AMBN mutations causing hypoplastic amelogenesis imperfecta and Ambn knockout-NLS-laczknockin mice exhibiting failed amelogenesis and Ambn tissue-specificity. Mol. Genet. Genomic Med. 2019; 7(9): e929.
24. Lu T; Li M; Xu X; Xiong J; Huang C; Zhang X; Hu A; Peng L; Cai D; Zhang L; Wu B; Xiong F. Whole exome sequencing identifies an AMBN missense mutation causing severe autosomal-dominant amelogenesis imperfecta and dentin disorders. Int. J. Oral Sci. 2018; 10(3): 26.
25. Wang S.K; Zhang H; Hu C.Y; Liu J.F; Chadha S; Kim J.W; Simmer J.P; Hu J.C.C. FAM83H and autosomal dominant hypocalcified amelogenesis imperfecta. J. Dent. Res. 2021; 100(3): 293-301.
26. Urzua B; Martinez C; Ortega-Pinto A; Adorno D; Morales-Bozo I; Riadi G; Jara L; Plaza A; Lefimil C; Lozano C; Reyes M. Novel missense mutation of the FAM83H gene causes retention of amelogenin and a mild clinical phenotype of hypocalcified enamel. Arch. Oral Biol. 2015; 60(9): 1356-1367.
27. Wang S.K; Hu Y; Yang J; Smith C.E; Richardson A.S; Yamakoshi Y; Lee Y.L; Seymen F; Koruyucu M; Gencay K; Lee M; Choi M; Kim J.W; Hu J.C.C; Simmer J.P. Fam83h null mice support a neomorphic mechanism for human ADHCAI. Mol. Genet. Genomic Med. 2015; 4(1): 46-67.
28. Wang S.K; Hu Y; Smith C.E; Yang J; Zeng C; Kim J.W; Hu J.C.C; Simmer J.P. The enamel phenotype in homozygous Fam83h truncation mice. Mol. Genet. Genomic Med. 2019; 7(6): e724.
29. Zheng, Y; Lu T; Chen J; Li M; Xiong J; He F; Gan Z; Guo Y; Zhang L; Xiong F. The gain-of-function FAM83H mutation caused hypocalcification amelogenesis imperfecta in a chinese family. Clin. Oral Invest. 2021; 25(5): 2915-2923.
30. Xin W; Wenjun W; Man Q; Yuming Z. Novel FAM83H mutations in patients with amelogenesis imperfecta. Sci. Rep. 2017; 7(1): 6075.
31. Yu S; Quan J; Wang X; Sun X; Zhang X; Liu Y; Zhang C; Zheng S. A novel FAM83H mutation in one Chinese family with autosomal-dominant hypocalcification amelogenesis imperfecta. Mutagenesis. 2018; 33(4): 333-340.
32. Zhang C; Song Y; Bian Z; Ultrastructural analysis of the teeth affected with amelogenesis imperfecta resulting from FAM83H mutations and review of the literatures. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2015; 119(2): e69-76.
33. Kuga T; Sasaki M; Mikami T; Miake Y; Adachi J; Shimizu M; Saito Y; Koura M; Takeda Y; Matsuda J; Tomonaga T; Nakayama Y. FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes. Sci. Rep. 2016; 6: 26557.
34. Gasse B; Prasad M; Delgado S; Huckert M; Kawczynski M; Garret-Bernardin A; Lopez-Cazaux S; Bailleul-Forestier I; Manière M.C; Stoetzel C; Bloch-Zupan A; Sire J.Y. Evolutionary analysis predicts sensitive positions of MMP20 and validates newly-and previously-identified MMP20 mutations causing amelogenesis imperfecta. Front. Physiol. 2017; 8: 398.
35. Wang S.K; Zhang H; Chavez M.B; Hu Y; Seymen F; Koruyucu M; Kasimoglu Y; Colvin C.D; Kolli T.N; Tan M.H; Wang Y.L; Lu P.Y; Kim J.W; Foster B.L; Bartlett J.D; Simmer J.P; Hu J.C.C. Dental malformations associated with biallelic MMP20 mutations. Mol. Genet. Genomic Med. 2020; 8(8): e1307.
36. Seymen F; Park J.C; Lee K.E; Lee H.K; Lee D.S; Koruyucu M; Gencay K; Bayram M; Tuna E.B; Lee Z.H; Kim Y.J; Kim J.W. Novel MMP20 and KLK4 mutations in amelogenesis imperfecta. J. Dent. Res. 2015; 94(8): 1063-1069.
37. Kim Y.J; Kang J; Seymen F; Koruyucu M; Zhang H; Kasimoglu Y; Bayram M; Tuna-Ince E.B; Bayrak
S; Tuloglu N; Hu J.C.C; Simmer J.P; Kim J.W. Alteration of exon definition causes amelogenesis imperfecta. J. Dent. Res. 2020; 99(4): 410-418.
38. Kim Y.J; Kang J; Seymen F; Koruyucu M; Gencay K; Shin T.J; Hyun H.K; Lee Z.H; Hu J.C.C; Simmer J.P; Kim J.W. Analyses of MMP20 missense mutations in two families with hypomaturation amelogenesis imperfecta. Front. Physiol. 2017; 8: 229.
39. Hu Y; Smith C.E; Richardson A.S; Bartlett J.D; Hu J.C; Simmer J.P. MMP20, KLK4, and MMP20/KLK4 double null mice define roles for matrix proteases during dental enamel formation. Mol. Genet. Genomic Med. 2015; 4(2): 178-196.
40. Smith C.E.L; Kirkham J; Day P.F; Soldani F; mcderra E.J; Poulter J.A; Inglehearn C.F; Mighell A.J; Brookes S.J. A fourth KLK4 mutation is associated with enamel hypomineralisation and structural abnormalities. Front. Physiol. 2017; 8: 333.
41. Hart P.S; Hart T.C; Michalec M.D; Ryu, O.H; Simmons D; Hong S; Wright J.T. Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. J. Med. Genet. 2004; 41(7): 545-549.
42. Wang S.K; Hu Y; Simmer J.P; Seymen F; Estrella N.M.R.P; Pal S; Reid B.M; Yildirim M; Bayram M; Bartlett J.D; Hu J.C.C. Novel KLK4 and MMP20 mutations discovered by whole-exome sequencing. J. Dent. Res. 2013; 92(3): 266-271.