- Email: [email protected]
Thickness and microhardness of deciduous tooth enamel with known DLX3 mutation
archives of oral biology 54 (2009) 830–834
available at www.sciencedirect.com
journal homepage: www.intl.elsevierhealth.com/journals/arob
Thickness and microhardness of deciduous tooth enamel with known DLX3 mutation Hong-Keun Hyun a, Jung-Wook Kim a,b,* a
Department of Pediatric Dentistry, Dental Research Institute and BK21 Program, School of Dentistry, Seoul National University, Seoul, South Korea b Department of Cell and Developmental Biology, Dental Research Institute and BK21 Program, School of Dentistry, Seoul National University, Seoul, South Korea
article info
abstract
Article history:
Aim: To investigate the thickness and hardness of teeth affected by a 2-bp deletion
Accepted 16 June 2009
(c.561_562delCT) in the DLX3 gene. Methods and materials: Extracted maxillary deciduous second molar was collected from the
Keywords:
affected individual at age 12 years 7 months. Samples were sectioned buccolingually after
Enamel
embedding in epoxy resin. We measured the enamel thickness and microhardness and
DLX3
performed an elemental analysis using an electron probe microanalyser.
Thickness
Results: On average, the hardness of the enamel with a 2-bp deletion in DLX3 was about 53%
Microhardness
of normal enamel hardness. The mutant enamel thickness was about half of the thickness
Mutation
of the normal control. The calcium level in the enamel with the 2-bp deletion was slightly decreased, while the magnesium level was slightly increased, in comparison to levels measured for normal teeth. Conclusion: This study shows that enamel affected by a 2-bp deletion in DLX3 has reduced thickness as well as diminished microhardness. These data may explain the severe attrition and interdental spacing observed in affected individuals. # 2009 Elsevier Ltd. All rights reserved.
1.
Introduction
The distal-less homeobox 3 (DLX3) gene, located on chromosome 17q21, is a homeobox gene with a crucial role during embryonic development.1 It has been shown that a 4-bp deletion (c.571_574delGGGG) in this gene results in trichodento-osseous syndrome (TDO; OMIM 190320).2 TDO syndrome is characterized by defects in hair, teeth and bone, with an autosomal dominant inheritance pattern.1,3 The main clinical features include unique curly or kinky hair at birth that eventually straightens in many cases, enamel hypoplasia with taurodontism, and increased bone density.4
The case with c.561_562delCT in the DLX3 gene reported by Dong et al. resulted in only enamel phenotype (hypoplastichypomaturation amelogenesis imperfecta with taurodontism, AIHHT; OMIM 104510) while the same mutation identified independently in two families of different ethnic background was responsible for the classic TDO.5 Thus it has been debated whether this novel 2-bp deletion in the DLX3 gene causes nonoral symptoms, such as defects in the hair, increased bone density or nail involvement. Dental phenotypes such as taurodontism, enamel thickness and mineral content have been reported for the TDO syndrome associated with the 4-bp deletion in the DLX3
* Corresponding author at: Department of Pediatric Dentistry, Department of Cell and Developmental Biology, Dental Research Institute and BK21 Program, School of Dentistry, Seoul National University, 275-1 Yongon-dong, Chongno-gu, Seoul 110-768, South Korea. Tel.: +82 2 2072 2639; fax: +82 2 744 3599. E-mail address: [email protected] (J.-W. Kim). 0003–9969/$ – see front matter # 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.archoralbio.2009.06.005
archives of oral biology 54 (2009) 830–834
gene,3,6 but the tooth characteristics associated with the 2-bp deletion in DLX3 have not yet been reported. Therefore, in this study, we measured the enamel thickness, microhardness and elemental content of a primary maxillary second molar with a 2-bp deletion in the DLX3 gene.
2.
Materials and methods
This experiment was undertaken with the understanding and written consent of the patient according to the Declaration of Helsinki. The study protocol was independently reviewed and approved by the Institution Review Board at the Seoul National University Dental Hospital.
2.1.
Samples
A deciduous right maxillary second molar was collected from a male patient with a known DLX3 mutation (c.561_562delCT) at age 12 years 7 months. Control teeth (deciduous maxillary second molars) were collected from normal controls of the same gender at similar age.
2.2.
Microhardness
The deciduous tooth was embedded in the epoxy resin and cut using a rotary diamond saw. The tooth was then sectioned buccolingually at the mesiobuccal and distobuccal cusps. For this test, six control teeth were used. Samples were polished using 200, 600, 800, 1000 and 2000 grit SiC papers. The microhardness score was measured at six points (enamel; near surface, middle, near DEJ, dentin; near DEJ, middle, pulpal). The measurement of the microhardness was performed four times at each point. Vickers microhardness (VHN) was measured using a microhardness tester (HMV-2, Schimadzu, Japan) where a 4.903 N load was applied for 10 s to obtain the measurement.
2.3.
831
Enamel thickness
Sections were carbon-coated using a carbon coater (CC7650, Quorum technologies, UK) and SEM image was taken at 30 magnification using a field emission scanning electron microscope (S-4700, Hitachi, Japan). For this test, six control teeth were used and the measurement was repeated five times. Maximal enamel thickness perpendicular to DEJ was measured using image J (version 1.41, NIH, USA) on the buccal and labial slopes excluding cuspal area due to attrition.
2.4.
Electron probe microanalysis
Elemental microanalyses were performed using an Electron Probe Micro Analyzer (JXA-8900R, JEOL, Tokyo, Japan) equipped with Wavelength Dispersive X-ray Spectroscopy (WDS). The standards used for calibration were Apatite [Ca5(PO4)5(F,Cl)], Indium phosphide (InP) and Periclase (MgO) for calcium, phosphate and magnesium, respectively. The counting time at each point was 20 s with a 1 mm diameter of the electron beam at 15.0 kV and 10 nA. For this test, three normal samples were used. Measurements were performed at six points (enamel; near surface, middle, near DEJ, dentin; near DEJ, middle, pulpal). Three-spot (about 50 mm distance) measurements were performed at each point.
3.
Results
3.1.
Microhardness
The microhardness value of the DLX3 mutant enamel was very low compared to that of the normal enamel (less than 95% confidence interval). On average, the hardness of the DLX3 mutant enamel was about 53% of the hardness of normal enamel. However, the microhardness value of the DLX3 mutant dentin was similar to that of normal dentin (Fig. 1).
Fig. 1 – Microhardness of normal and affected teeth. The Vickers microhardness number (VHN) is indicated in the box. The 95% confidence interval is indicated in the box for the normal teeth. Standard deviation is indicated in the box for the 2-bp mutant DLX3 teeth.
832
archives of oral biology 54 (2009) 830–834
Fig. 2 – Thickness of the enamel. Cross-sectional SEM image of the 2-bp mutant DLX3 teeth (upper left) and normal control (upper right). The 95% confidence interval is indicated in the box for normal teeth.
3.2.
Enamel thickness
The enamel thickness of the DLX3 mutant tooth was decreased to about 50% of the thickness of the normal teeth (Fig. 2).
3.3.
Electron probe microanalysis
The calcium level in the DLX3 mutant enamel was slightly decreased compared to that of normal teeth. The phosphate level and Ca/P atomic ratio were not significantly different
Fig. 3 – Elemental composition of normal and affected teeth. Calcium (Ca), phosphate (P), magnesium (Mg), Ca/P ratio and Mg/P ratio are shown in separate graphs. The 95% confidence interval is indicated in the box for normal teeth. wt.% means percent in weight.
archives of oral biology 54 (2009) 830–834
between mutant and normal teeth. The magnesium level in the enamel was slightly increased in the DLX3 mutant tooth compared to normal teeth. However, the DLX3 mutant tooth had slightly decreased magnesium levels in the centre and pulpal areas of the dentin, in comparison to normal teeth (Fig. 3).
833
enamel microhardness. Further, the 2-bp deletion resulted in a slight decrease in calcium levels and a slight increase in magnesium levels in the enamel, in comparison to normal teeth.
Acknowledgments 4.
Discussion
DLX3 is expressed in the ameloblasts throughout presecretory, secretory and maturation stages of enamel formation.7 The enamel defects found among the TDO individuals with DLX3 mutation suggested a functional significance of DLX3 during enamel formation. The effect of a 4-bp deletion in the DLX3 gene has been thoroughly investigated and was found to have a dominant negative effect on wildtype DLX3.1 However little is known about the effect of a 2-bp deletion on the function of the DLX3 gene. Previous studies have shown that the 2-bp deletion in DLX3 exhibits defects in the enamel as well as other tissues, such as hair and nail, as in the TDO syndrome.8,9 However, the clinical manifestations of 2-bp deletional mutation are different from those of the 4-bp deletion. Taurodontism, an almost fully penetrating feature in TDO syndrome, is very mild or absent in many cases. Increased bone density, which can be identified in a lateral cephalometric radiograph in TDO syndrome, is not noticeable. It has been reported that the TDO syndrome associated with the 4-bp deletion in the DLX3 gene results in a pitted hypoplastic enamel surface with reduced enamel thickness (about 10–60% the thickness of control enamel), and hypomineralization of the enamel was not significant in most of the TDO enamel samples.6,10 This study shows that the deciduous enamel affected by the 2-bp deletion in DLX3 (c.561_562delCT) has reduced thickness as well as diminished enamel microhardness. The reduction in the thickness of the affected enamel could be explained by the regulation of amelogenin, a major enamel matrix protein, expression by the DLX homeoproteins.7,11 However the dentin microhardness appears unaffected by the mutation. This could be explained by the downregulation of DLX3 expression during odontoblast terminal differentiation (absence of DLX3 expression in secretory odontoblasts).12 Further, the 2-bp deletion resulted in a slight decrease in calcium levels and a slight increase in magnesium levels in the enamel, in comparison to normal teeth. Taken together, these data can explain the severe attrition and interdental spacing identified in the individual with the 2-bp deletion in DLX3.8 It is still unknown whether TDO syndrome and AIHHT are separate diseases with some common features or the same disease with different phenotypes. A functional analysis of the mutation and mutational analysis of the reported AIHHT families should clarify the nature and pathogenesis of these diseases.
5.
Conclusion
The deciduous enamel affected by the 2-bp deletion in DLX3 (c.561_562delCT) has reduced thickness as well as diminished
This work was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A060010), a grant from the Korea Science and Engineering Foundation (KOSEF) through the Biotechnology R&D program (No. M10646010003-08N4601-00310), and a grant from the Korea Science and Engineering Foundation (KOSEF) Science Research Center funded by the Korean Ministry of Education, Science and Technology (MEST) through the Bone Metabolism Research Center (No. R112008-023-02003-0). Competing interests: None declared. Ethical approval: The study protocol was independently reviewed and approved by the Institution Review Board at the Seoul National University Dental Hospital (CRI05003G).
references
1. Duverger O, Lee D, Hassan MQ, Chen SX, Jaisser F, Lian JB, et al. Molecular consequences of a frameshifted DLX3 mutant leading to Tricho-Dento-Osseous syndrome. J Biol Chem 2008;283:20198–208. 2. Price JA, Bowden DW, Wright JT, Pettenati MJ, Hart TC. Identification of a mutation in DLX3 associated with tricho-dento-osseous (TDO) syndrome. Hum Mol Genet 1998;7:563–9. 3. Wright JT, Kula K, Hall K, Simmons JH, Hart TC. Analysis of the tricho-dento-osseous syndrome genotype and phenotype. Am J Med Genet 1997;72: 197–204. 4. Price JA, Wright JT, Walker SJ, Crawford PJ, Aldred MJ, Hart TC. Tricho-dento-osseous syndrome and amelogenesis imperfecta with taurodontism are genetically distinct conditions. Clin Genet 1999;56:35–40. 5. Dong J, Amor D, Aldred MJ, Gu T, Escamilla M, MacDougall M. DLX3 mutation associated with autosomal dominant amelogenesis imperfecta with taurodontism. Am J Med Genet A 2005;133:138–41. 6. Spangler GS, Hall KI, Kula K, Hart TC, Wright JT. Enamel structure and composition in the tricho-dento-osseous syndrome. Connect Tissue Res 1998;39:165–75. discussion 87–94. 7. Lezot F, Thomas B, Greene SR, Hotton D, Yuan ZA, Castaneda B, et al. Physiological implications of DLX homeoproteins in enamel formation. J Cell Physiol 2008;216:688–97. 8. Lee SK, Lee ZH, Lee SJ, Ahn BD, Kim YJ, Lee SH, et al. DLX3 mutation in a new family and its phenotypic variations. J Dent Res 2008;87:354–7. 9. Wright JT, Hong SP, Simmons D, Daly B, Uebelhart D, Luder HU. DLX3 c.561_562delCT mutation causes attenuated phenotype of tricho-dento-osseous syndrome. Am J Med Genet A 2008;146:343–9. 10. Wright JT, Roberts MW, Wilson AR, Kudhail R. Tricho-dentoosseous syndrome. Features of the hair and teeth. Oral Surg Oral Med Oral Pathol 1994;77:487–93.
834
archives of oral biology 54 (2009) 830–834
11. Snead ML, Luo W, Lau EC, Slavkin HC. Spatial- and temporal-restricted pattern for amelogenin gene expression during mouse molar tooth organogenesis. Development 1988;104:77–85.
12. Ghoul-Mazgar S, Hotton D, Lezot F, Blin-Wakkach C, Asselin A, Sautier JM, et al. Expression pattern of DLX3 during cell differentiation in mineralized tissues. Bone 2005;37:799–809.
available at www.sciencedirect.com
journal homepage: www.intl.elsevierhealth.com/journals/arob
Thickness and microhardness of deciduous tooth enamel with known DLX3 mutation Hong-Keun Hyun a, Jung-Wook Kim a,b,* a
Department of Pediatric Dentistry, Dental Research Institute and BK21 Program, School of Dentistry, Seoul National University, Seoul, South Korea b Department of Cell and Developmental Biology, Dental Research Institute and BK21 Program, School of Dentistry, Seoul National University, Seoul, South Korea
article info
abstract
Article history:
Aim: To investigate the thickness and hardness of teeth affected by a 2-bp deletion
Accepted 16 June 2009
(c.561_562delCT) in the DLX3 gene. Methods and materials: Extracted maxillary deciduous second molar was collected from the
Keywords:
affected individual at age 12 years 7 months. Samples were sectioned buccolingually after
Enamel
embedding in epoxy resin. We measured the enamel thickness and microhardness and
DLX3
performed an elemental analysis using an electron probe microanalyser.
Thickness
Results: On average, the hardness of the enamel with a 2-bp deletion in DLX3 was about 53%
Microhardness
of normal enamel hardness. The mutant enamel thickness was about half of the thickness
Mutation
of the normal control. The calcium level in the enamel with the 2-bp deletion was slightly decreased, while the magnesium level was slightly increased, in comparison to levels measured for normal teeth. Conclusion: This study shows that enamel affected by a 2-bp deletion in DLX3 has reduced thickness as well as diminished microhardness. These data may explain the severe attrition and interdental spacing observed in affected individuals. # 2009 Elsevier Ltd. All rights reserved.
1.
Introduction
The distal-less homeobox 3 (DLX3) gene, located on chromosome 17q21, is a homeobox gene with a crucial role during embryonic development.1 It has been shown that a 4-bp deletion (c.571_574delGGGG) in this gene results in trichodento-osseous syndrome (TDO; OMIM 190320).2 TDO syndrome is characterized by defects in hair, teeth and bone, with an autosomal dominant inheritance pattern.1,3 The main clinical features include unique curly or kinky hair at birth that eventually straightens in many cases, enamel hypoplasia with taurodontism, and increased bone density.4
The case with c.561_562delCT in the DLX3 gene reported by Dong et al. resulted in only enamel phenotype (hypoplastichypomaturation amelogenesis imperfecta with taurodontism, AIHHT; OMIM 104510) while the same mutation identified independently in two families of different ethnic background was responsible for the classic TDO.5 Thus it has been debated whether this novel 2-bp deletion in the DLX3 gene causes nonoral symptoms, such as defects in the hair, increased bone density or nail involvement. Dental phenotypes such as taurodontism, enamel thickness and mineral content have been reported for the TDO syndrome associated with the 4-bp deletion in the DLX3
* Corresponding author at: Department of Pediatric Dentistry, Department of Cell and Developmental Biology, Dental Research Institute and BK21 Program, School of Dentistry, Seoul National University, 275-1 Yongon-dong, Chongno-gu, Seoul 110-768, South Korea. Tel.: +82 2 2072 2639; fax: +82 2 744 3599. E-mail address: [email protected] (J.-W. Kim). 0003–9969/$ – see front matter # 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.archoralbio.2009.06.005
archives of oral biology 54 (2009) 830–834
gene,3,6 but the tooth characteristics associated with the 2-bp deletion in DLX3 have not yet been reported. Therefore, in this study, we measured the enamel thickness, microhardness and elemental content of a primary maxillary second molar with a 2-bp deletion in the DLX3 gene.
2.
Materials and methods
This experiment was undertaken with the understanding and written consent of the patient according to the Declaration of Helsinki. The study protocol was independently reviewed and approved by the Institution Review Board at the Seoul National University Dental Hospital.
2.1.
Samples
A deciduous right maxillary second molar was collected from a male patient with a known DLX3 mutation (c.561_562delCT) at age 12 years 7 months. Control teeth (deciduous maxillary second molars) were collected from normal controls of the same gender at similar age.
2.2.
Microhardness
The deciduous tooth was embedded in the epoxy resin and cut using a rotary diamond saw. The tooth was then sectioned buccolingually at the mesiobuccal and distobuccal cusps. For this test, six control teeth were used. Samples were polished using 200, 600, 800, 1000 and 2000 grit SiC papers. The microhardness score was measured at six points (enamel; near surface, middle, near DEJ, dentin; near DEJ, middle, pulpal). The measurement of the microhardness was performed four times at each point. Vickers microhardness (VHN) was measured using a microhardness tester (HMV-2, Schimadzu, Japan) where a 4.903 N load was applied for 10 s to obtain the measurement.
2.3.
831
Enamel thickness
Sections were carbon-coated using a carbon coater (CC7650, Quorum technologies, UK) and SEM image was taken at 30 magnification using a field emission scanning electron microscope (S-4700, Hitachi, Japan). For this test, six control teeth were used and the measurement was repeated five times. Maximal enamel thickness perpendicular to DEJ was measured using image J (version 1.41, NIH, USA) on the buccal and labial slopes excluding cuspal area due to attrition.
2.4.
Electron probe microanalysis
Elemental microanalyses were performed using an Electron Probe Micro Analyzer (JXA-8900R, JEOL, Tokyo, Japan) equipped with Wavelength Dispersive X-ray Spectroscopy (WDS). The standards used for calibration were Apatite [Ca5(PO4)5(F,Cl)], Indium phosphide (InP) and Periclase (MgO) for calcium, phosphate and magnesium, respectively. The counting time at each point was 20 s with a 1 mm diameter of the electron beam at 15.0 kV and 10 nA. For this test, three normal samples were used. Measurements were performed at six points (enamel; near surface, middle, near DEJ, dentin; near DEJ, middle, pulpal). Three-spot (about 50 mm distance) measurements were performed at each point.
3.
Results
3.1.
Microhardness
The microhardness value of the DLX3 mutant enamel was very low compared to that of the normal enamel (less than 95% confidence interval). On average, the hardness of the DLX3 mutant enamel was about 53% of the hardness of normal enamel. However, the microhardness value of the DLX3 mutant dentin was similar to that of normal dentin (Fig. 1).
Fig. 1 – Microhardness of normal and affected teeth. The Vickers microhardness number (VHN) is indicated in the box. The 95% confidence interval is indicated in the box for the normal teeth. Standard deviation is indicated in the box for the 2-bp mutant DLX3 teeth.
832
archives of oral biology 54 (2009) 830–834
Fig. 2 – Thickness of the enamel. Cross-sectional SEM image of the 2-bp mutant DLX3 teeth (upper left) and normal control (upper right). The 95% confidence interval is indicated in the box for normal teeth.
3.2.
Enamel thickness
The enamel thickness of the DLX3 mutant tooth was decreased to about 50% of the thickness of the normal teeth (Fig. 2).
3.3.
Electron probe microanalysis
The calcium level in the DLX3 mutant enamel was slightly decreased compared to that of normal teeth. The phosphate level and Ca/P atomic ratio were not significantly different
Fig. 3 – Elemental composition of normal and affected teeth. Calcium (Ca), phosphate (P), magnesium (Mg), Ca/P ratio and Mg/P ratio are shown in separate graphs. The 95% confidence interval is indicated in the box for normal teeth. wt.% means percent in weight.
archives of oral biology 54 (2009) 830–834
between mutant and normal teeth. The magnesium level in the enamel was slightly increased in the DLX3 mutant tooth compared to normal teeth. However, the DLX3 mutant tooth had slightly decreased magnesium levels in the centre and pulpal areas of the dentin, in comparison to normal teeth (Fig. 3).
833
enamel microhardness. Further, the 2-bp deletion resulted in a slight decrease in calcium levels and a slight increase in magnesium levels in the enamel, in comparison to normal teeth.
Acknowledgments 4.
Discussion
DLX3 is expressed in the ameloblasts throughout presecretory, secretory and maturation stages of enamel formation.7 The enamel defects found among the TDO individuals with DLX3 mutation suggested a functional significance of DLX3 during enamel formation. The effect of a 4-bp deletion in the DLX3 gene has been thoroughly investigated and was found to have a dominant negative effect on wildtype DLX3.1 However little is known about the effect of a 2-bp deletion on the function of the DLX3 gene. Previous studies have shown that the 2-bp deletion in DLX3 exhibits defects in the enamel as well as other tissues, such as hair and nail, as in the TDO syndrome.8,9 However, the clinical manifestations of 2-bp deletional mutation are different from those of the 4-bp deletion. Taurodontism, an almost fully penetrating feature in TDO syndrome, is very mild or absent in many cases. Increased bone density, which can be identified in a lateral cephalometric radiograph in TDO syndrome, is not noticeable. It has been reported that the TDO syndrome associated with the 4-bp deletion in the DLX3 gene results in a pitted hypoplastic enamel surface with reduced enamel thickness (about 10–60% the thickness of control enamel), and hypomineralization of the enamel was not significant in most of the TDO enamel samples.6,10 This study shows that the deciduous enamel affected by the 2-bp deletion in DLX3 (c.561_562delCT) has reduced thickness as well as diminished enamel microhardness. The reduction in the thickness of the affected enamel could be explained by the regulation of amelogenin, a major enamel matrix protein, expression by the DLX homeoproteins.7,11 However the dentin microhardness appears unaffected by the mutation. This could be explained by the downregulation of DLX3 expression during odontoblast terminal differentiation (absence of DLX3 expression in secretory odontoblasts).12 Further, the 2-bp deletion resulted in a slight decrease in calcium levels and a slight increase in magnesium levels in the enamel, in comparison to normal teeth. Taken together, these data can explain the severe attrition and interdental spacing identified in the individual with the 2-bp deletion in DLX3.8 It is still unknown whether TDO syndrome and AIHHT are separate diseases with some common features or the same disease with different phenotypes. A functional analysis of the mutation and mutational analysis of the reported AIHHT families should clarify the nature and pathogenesis of these diseases.
5.
Conclusion
The deciduous enamel affected by the 2-bp deletion in DLX3 (c.561_562delCT) has reduced thickness as well as diminished
This work was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A060010), a grant from the Korea Science and Engineering Foundation (KOSEF) through the Biotechnology R&D program (No. M10646010003-08N4601-00310), and a grant from the Korea Science and Engineering Foundation (KOSEF) Science Research Center funded by the Korean Ministry of Education, Science and Technology (MEST) through the Bone Metabolism Research Center (No. R112008-023-02003-0). Competing interests: None declared. Ethical approval: The study protocol was independently reviewed and approved by the Institution Review Board at the Seoul National University Dental Hospital (CRI05003G).
references
1. Duverger O, Lee D, Hassan MQ, Chen SX, Jaisser F, Lian JB, et al. Molecular consequences of a frameshifted DLX3 mutant leading to Tricho-Dento-Osseous syndrome. J Biol Chem 2008;283:20198–208. 2. Price JA, Bowden DW, Wright JT, Pettenati MJ, Hart TC. Identification of a mutation in DLX3 associated with tricho-dento-osseous (TDO) syndrome. Hum Mol Genet 1998;7:563–9. 3. Wright JT, Kula K, Hall K, Simmons JH, Hart TC. Analysis of the tricho-dento-osseous syndrome genotype and phenotype. Am J Med Genet 1997;72: 197–204. 4. Price JA, Wright JT, Walker SJ, Crawford PJ, Aldred MJ, Hart TC. Tricho-dento-osseous syndrome and amelogenesis imperfecta with taurodontism are genetically distinct conditions. Clin Genet 1999;56:35–40. 5. Dong J, Amor D, Aldred MJ, Gu T, Escamilla M, MacDougall M. DLX3 mutation associated with autosomal dominant amelogenesis imperfecta with taurodontism. Am J Med Genet A 2005;133:138–41. 6. Spangler GS, Hall KI, Kula K, Hart TC, Wright JT. Enamel structure and composition in the tricho-dento-osseous syndrome. Connect Tissue Res 1998;39:165–75. discussion 87–94. 7. Lezot F, Thomas B, Greene SR, Hotton D, Yuan ZA, Castaneda B, et al. Physiological implications of DLX homeoproteins in enamel formation. J Cell Physiol 2008;216:688–97. 8. Lee SK, Lee ZH, Lee SJ, Ahn BD, Kim YJ, Lee SH, et al. DLX3 mutation in a new family and its phenotypic variations. J Dent Res 2008;87:354–7. 9. Wright JT, Hong SP, Simmons D, Daly B, Uebelhart D, Luder HU. DLX3 c.561_562delCT mutation causes attenuated phenotype of tricho-dento-osseous syndrome. Am J Med Genet A 2008;146:343–9. 10. Wright JT, Roberts MW, Wilson AR, Kudhail R. Tricho-dentoosseous syndrome. Features of the hair and teeth. Oral Surg Oral Med Oral Pathol 1994;77:487–93.
834
archives of oral biology 54 (2009) 830–834
11. Snead ML, Luo W, Lau EC, Slavkin HC. Spatial- and temporal-restricted pattern for amelogenin gene expression during mouse molar tooth organogenesis. Development 1988;104:77–85.
12. Ghoul-Mazgar S, Hotton D, Lezot F, Blin-Wakkach C, Asselin A, Sautier JM, et al. Expression pattern of DLX3 during cell differentiation in mineralized tissues. Bone 2005;37:799–809.