Targeted Genetic Education in Dentistry in the Era of Genomics

Abstract

Background: The growing body of knowledge on the human genome and its variants points towards the significance of genetic factors in oral health and disease. Since the dental curricula have historically prioritized clinically oriented subjects, this focus has resulted in insufficient coverage of genetics. To leverage this knowledge in patient care, dental education must equip students with an understanding of the principles of genetics. Method: We have established "Genetic Educators Network in Dentistry" (GEN-Dent) to identify common concerns regarding genetics in dental education and work for a greater emphasis on genetics in future dental programs to make sure that professionals in dentistry are well-prepared to navigate the complexities of the evolving "human genome era". Results: Here, GEN-Dent proposes specific learning goals for medical genetics in dentistry and provides supporting teaching material addressing each learning goal. The five life-like case studies exemplify different dental conditions and introduce important concepts of genetics, inspiring other educators. Conclusions: Opportunities in Scandinavian countries can be an advantage in increasing global awareness of the importance of genetics in dentistry. The integration of genetics into dental education not only aims to improve patient care but also seeks to inspire a new generation of basic scientists with clinical backgrounds in dentistry. We expect that using life-like patient cases will significantly motivate dental students when learning medical genetics.

Keywords: case study; dental genetics; dentistry; genomics; learning goals; next-generation sequencing; teaching genetics; teeth.

Figure 1

Case suggestions for medical genetics for dentistry students. Five examples of cases introducing key concepts of medical genetics through life-like patient stories, as they could be experienced in a dentist’s clinic or a hospital. (A) Amelogenesis Imperfecta. Keywords: Autosomal Dominant, Reduced Penetrance, Locus Heterogeneity, Genes Regulating Enamel Formation, Nonsense Mutation. The case introduces the students to drawing and analyzing a pedigree. Mode of inheritance is most likely autosomal dominant due to the phenotype appearing in father and son; however, this means that the mother of the proband presents reduced penetrance. A gene panel analysis is performed due to locus heterogeneity. The analysis reveals heterozygosity for a nonsense mutation in the ENAM gene as described in Seymen et al. 2014 [29]. (B) Hypohidrotic Ectodermal Dysplasia. Keywords: Locus Heterogeneity, Autosomal Recessive, X-linked Recessive, Risk Assessment using Hardy–Weinberg, X-chromosome Inactivation, Genes Regulating Tooth Formation, Missense Mutation. The pedigree of the proband indicates different modes of inheritance in her and her husband’s families. The risk assessment for the unborn child is performed for each HED form individually. The risk for the X-linked recessive form in the mother’s family is 1/8, as the maternal grandmother is a carrier, and only boys will be affected. The risk for the autosomal recessive form found in the father’s family is 0.0000033 as the carrier risk of the father is 2/3 and of the mother 0.00002 (based on Hardy–Weinberg calculation where q² = 1/100,000 leads to 2 pq = 0.00002). The sister of the proband has a 0.5 risk of being a carrier. Non-random X-chromosome inactivation is most likely the reason why she presents with weak symptoms [30]. Illustration of patient by Malin Bernas-Theisen, TAKO-Center. (C) Nevoid Basal Cell Carcinoma, Gorlin syndrome. Keywords: Hereditary Cancer of the Jaw and Skin, Autosomal Dominant, Knudson’s Two-Hit Model, SNP Linked to the Gene. Gorlin syndrome (GS) is characterized by odontogenic keratocysts as well as early-onset of multiple basal cell carcinomas. GS may be caused by inherited loss-of-function mutations in the PTCH1 gene as presented in the case. Family history indicates autosomal dominant mode of inheritance, which is confirmed by findings of heterozygosity for a nonsense mutation in PTCH1 in the blood of the proband. Analysis of tumor tissue from the proband shows loss of heterozygosity for both the PTCH1 mutation [31] as well as a closely linked single nucleotide polymorphism [32], indicating somatic deletion of the PTCH1 region (including the SNP) as a second hit according to Knudson’s Two-Hit model. (D) Molar–Incisor Hypomineralization. Keywords: Multifactorial Polygenic Inheritance, SNPs in Genes Regulating Enamel Formation, Discordant Monozygotic Twins. The case story presents a family in which several cases of Molar–Incisor Hypomineralization (MIH) appear. Discordance for the phenotype in a pair of monozygotic twins indicates a multifactorial mode of inheritance. Analysis of two specific variants in the genes encoding ameloblastin and enamelysin suggests an association of the phenotype with the genotype indicating that these two genes are involved in the disease [33]. This may be linked to the role of the proteins encoded in the development of the enamel. Interestingly, loss-of-function DNA variants in the gene encoding ameloblastin (AMBN) may lead to Amelogenesis Imperfecta while increased expression of ameloblastin has been linked to Molar–Incisor Hypomineralization, allowing for discussion of the opposing effects of different DNA variants in the AMBN gene [34]. Environmental risk factors like early childhood infectious diseases might act through effecting the epigenetic regulation of gene expression [35]. (E) Chromosome 9p duplication and cleft lip and palate. Keywords: Unbalanced Reciprocal Translocation, Cleft Lip and Palate. A routine ultrasound scan of a fetus reveals a cleft lip and palate, which could be an indication of a chromosomal abnormality. Array-CGH and karyotyping of the fetus reveals an unbalanced 9;22 translocation leading to partial trisomy of the short arm of chromosome 9 (dup(9)(p12pter)). Discussion about the origin of this abnormality should lead to the understanding of a potential balanced translocation in one of the parents, indicating an increased recurrence risk in future offspring. A literature search will reveal a potential complex phenotype in the child [36], including a profound impact on teeth development. This specific case was developed as an interactive laboratory simulation in a collaboration between the University of Copenhagen and Labster ApS https://www.labster.com/. Karyograms were drawn using the CyDAS Package http://www.cydas.org/OnlineAnalysis/ accessed on 23 October 2024 [37].

Figure 1

Case suggestions for medical genetics for dentistry students. Five examples of cases introducing key concepts of medical genetics through life-like patient stories, as they could be experienced in a dentist’s clinic or a hospital. (A) Amelogenesis Imperfecta. Keywords: Autosomal Dominant, Reduced Penetrance, Locus Heterogeneity, Genes Regulating Enamel Formation, Nonsense Mutation. The case introduces the students to drawing and analyzing a pedigree. Mode of inheritance is most likely autosomal dominant due to the phenotype appearing in father and son; however, this means that the mother of the proband presents reduced penetrance. A gene panel analysis is performed due to locus heterogeneity. The analysis reveals heterozygosity for a nonsense mutation in the ENAM gene as described in Seymen et al. 2014 [29]. (B) Hypohidrotic Ectodermal Dysplasia. Keywords: Locus Heterogeneity, Autosomal Recessive, X-linked Recessive, Risk Assessment using Hardy–Weinberg, X-chromosome Inactivation, Genes Regulating Tooth Formation, Missense Mutation. The pedigree of the proband indicates different modes of inheritance in her and her husband’s families. The risk assessment for the unborn child is performed for each HED form individually. The risk for the X-linked recessive form in the mother’s family is 1/8, as the maternal grandmother is a carrier, and only boys will be affected. The risk for the autosomal recessive form found in the father’s family is 0.0000033 as the carrier risk of the father is 2/3 and of the mother 0.00002 (based on Hardy–Weinberg calculation where q² = 1/100,000 leads to 2 pq = 0.00002). The sister of the proband has a 0.5 risk of being a carrier. Non-random X-chromosome inactivation is most likely the reason why she presents with weak symptoms [30]. Illustration of patient by Malin Bernas-Theisen, TAKO-Center. (C) Nevoid Basal Cell Carcinoma, Gorlin syndrome. Keywords: Hereditary Cancer of the Jaw and Skin, Autosomal Dominant, Knudson’s Two-Hit Model, SNP Linked to the Gene. Gorlin syndrome (GS) is characterized by odontogenic keratocysts as well as early-onset of multiple basal cell carcinomas. GS may be caused by inherited loss-of-function mutations in the PTCH1 gene as presented in the case. Family history indicates autosomal dominant mode of inheritance, which is confirmed by findings of heterozygosity for a nonsense mutation in PTCH1 in the blood of the proband. Analysis of tumor tissue from the proband shows loss of heterozygosity for both the PTCH1 mutation [31] as well as a closely linked single nucleotide polymorphism [32], indicating somatic deletion of the PTCH1 region (including the SNP) as a second hit according to Knudson’s Two-Hit model. (D) Molar–Incisor Hypomineralization. Keywords: Multifactorial Polygenic Inheritance, SNPs in Genes Regulating Enamel Formation, Discordant Monozygotic Twins. The case story presents a family in which several cases of Molar–Incisor Hypomineralization (MIH) appear. Discordance for the phenotype in a pair of monozygotic twins indicates a multifactorial mode of inheritance. Analysis of two specific variants in the genes encoding ameloblastin and enamelysin suggests an association of the phenotype with the genotype indicating that these two genes are involved in the disease [33]. This may be linked to the role of the proteins encoded in the development of the enamel. Interestingly, loss-of-function DNA variants in the gene encoding ameloblastin (AMBN) may lead to Amelogenesis Imperfecta while increased expression of ameloblastin has been linked to Molar–Incisor Hypomineralization, allowing for discussion of the opposing effects of different DNA variants in the AMBN gene [34]. Environmental risk factors like early childhood infectious diseases might act through effecting the epigenetic regulation of gene expression [35]. (E) Chromosome 9p duplication and cleft lip and palate. Keywords: Unbalanced Reciprocal Translocation, Cleft Lip and Palate. A routine ultrasound scan of a fetus reveals a cleft lip and palate, which could be an indication of a chromosomal abnormality. Array-CGH and karyotyping of the fetus reveals an unbalanced 9;22 translocation leading to partial trisomy of the short arm of chromosome 9 (dup(9)(p12pter)). Discussion about the origin of this abnormality should lead to the understanding of a potential balanced translocation in one of the parents, indicating an increased recurrence risk in future offspring. A literature search will reveal a potential complex phenotype in the child [36], including a profound impact on teeth development. This specific case was developed as an interactive laboratory simulation in a collaboration between the University of Copenhagen and Labster ApS https://www.labster.com/. Karyograms were drawn using the CyDAS Package http://www.cydas.org/OnlineAnalysis/ accessed on 23 October 2024 [37].

Figure 1

Case suggestions for medical genetics for dentistry students. Five examples of cases introducing key concepts of medical genetics through life-like patient stories, as they could be experienced in a dentist’s clinic or a hospital. (A) Amelogenesis Imperfecta. Keywords: Autosomal Dominant, Reduced Penetrance, Locus Heterogeneity, Genes Regulating Enamel Formation, Nonsense Mutation. The case introduces the students to drawing and analyzing a pedigree. Mode of inheritance is most likely autosomal dominant due to the phenotype appearing in father and son; however, this means that the mother of the proband presents reduced penetrance. A gene panel analysis is performed due to locus heterogeneity. The analysis reveals heterozygosity for a nonsense mutation in the ENAM gene as described in Seymen et al. 2014 [29]. (B) Hypohidrotic Ectodermal Dysplasia. Keywords: Locus Heterogeneity, Autosomal Recessive, X-linked Recessive, Risk Assessment using Hardy–Weinberg, X-chromosome Inactivation, Genes Regulating Tooth Formation, Missense Mutation. The pedigree of the proband indicates different modes of inheritance in her and her husband’s families. The risk assessment for the unborn child is performed for each HED form individually. The risk for the X-linked recessive form in the mother’s family is 1/8, as the maternal grandmother is a carrier, and only boys will be affected. The risk for the autosomal recessive form found in the father’s family is 0.0000033 as the carrier risk of the father is 2/3 and of the mother 0.00002 (based on Hardy–Weinberg calculation where q² = 1/100,000 leads to 2 pq = 0.00002). The sister of the proband has a 0.5 risk of being a carrier. Non-random X-chromosome inactivation is most likely the reason why she presents with weak symptoms [30]. Illustration of patient by Malin Bernas-Theisen, TAKO-Center. (C) Nevoid Basal Cell Carcinoma, Gorlin syndrome. Keywords: Hereditary Cancer of the Jaw and Skin, Autosomal Dominant, Knudson’s Two-Hit Model, SNP Linked to the Gene. Gorlin syndrome (GS) is characterized by odontogenic keratocysts as well as early-onset of multiple basal cell carcinomas. GS may be caused by inherited loss-of-function mutations in the PTCH1 gene as presented in the case. Family history indicates autosomal dominant mode of inheritance, which is confirmed by findings of heterozygosity for a nonsense mutation in PTCH1 in the blood of the proband. Analysis of tumor tissue from the proband shows loss of heterozygosity for both the PTCH1 mutation [31] as well as a closely linked single nucleotide polymorphism [32], indicating somatic deletion of the PTCH1 region (including the SNP) as a second hit according to Knudson’s Two-Hit model. (D) Molar–Incisor Hypomineralization. Keywords: Multifactorial Polygenic Inheritance, SNPs in Genes Regulating Enamel Formation, Discordant Monozygotic Twins. The case story presents a family in which several cases of Molar–Incisor Hypomineralization (MIH) appear. Discordance for the phenotype in a pair of monozygotic twins indicates a multifactorial mode of inheritance. Analysis of two specific variants in the genes encoding ameloblastin and enamelysin suggests an association of the phenotype with the genotype indicating that these two genes are involved in the disease [33]. This may be linked to the role of the proteins encoded in the development of the enamel. Interestingly, loss-of-function DNA variants in the gene encoding ameloblastin (AMBN) may lead to Amelogenesis Imperfecta while increased expression of ameloblastin has been linked to Molar–Incisor Hypomineralization, allowing for discussion of the opposing effects of different DNA variants in the AMBN gene [34]. Environmental risk factors like early childhood infectious diseases might act through effecting the epigenetic regulation of gene expression [35]. (E) Chromosome 9p duplication and cleft lip and palate. Keywords: Unbalanced Reciprocal Translocation, Cleft Lip and Palate. A routine ultrasound scan of a fetus reveals a cleft lip and palate, which could be an indication of a chromosomal abnormality. Array-CGH and karyotyping of the fetus reveals an unbalanced 9;22 translocation leading to partial trisomy of the short arm of chromosome 9 (dup(9)(p12pter)). Discussion about the origin of this abnormality should lead to the understanding of a potential balanced translocation in one of the parents, indicating an increased recurrence risk in future offspring. A literature search will reveal a potential complex phenotype in the child [36], including a profound impact on teeth development. This specific case was developed as an interactive laboratory simulation in a collaboration between the University of Copenhagen and Labster ApS https://www.labster.com/. Karyograms were drawn using the CyDAS Package http://www.cydas.org/OnlineAnalysis/ accessed on 23 October 2024 [37].