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1.
Dent Traumatol ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38591807

RESUMO

BACKGROUND/AIMS: The preservation of avulsed teeth is critical in dental trauma management, necessitating effective storage media to ensure viable tooth reimplantation. The urgent need for accurate information has led both professional and non-professional individuals to increasingly seek guidance from video-sharing platforms such as YouTube™ and TikTok™. These platforms have become key resources for advice on such dental emergencies, but the reliability and accuracy of this information have not yet been systematically evaluated. This study aimed to assess the quality, accuracy, and reliability YouTube™ and TikTok™ of videos regarding storage solutions for avulsion injuries. MATERIAL AND METHODS: A search was conducted on YouTube™ and TikTok™ on February 4th, 2023, using terms related to traumatic dental injuries, and 53 videos were included. Video demographics such as platform, duration, type, upload date, likes, and comments were recorded. Video content quality, reliability, and accuracy were measured using the Global Quality Scale (GQS), Journal of the American Medical Association (JAMA) benchmarks, and Video Information and Quality Index (VIQI). Research data were analyzed using SPSS IBM 24.0 at a 95% confidence interval. RESULTS: In total, 53 videos were examined. The average scores were JAMA: 1.70/4.00, modified DISCERN: 54.3/80.00, GQS: 3.88/5.00, and VIQI: 13.8/20.00. According to the modified DISCERN index, there were no "very poor" or "poor" quality videos, 49.05% were "moderate," 22.6% were "good," and 28.3% were "very good." No difference was found between YouTube™ and TikTok™ videos in terms of the modified DISCERN index, JAMA scores, GQS, and VIQI scoring (p > .05). CONCLUSIONS: Traumatic dental injuries are a common problem among children, and evaluating the reliability of available contents is becoming crucial for appropriate intervention. The study reveals that despite being sourced mainly from dental professionals, the overall quality of videos on avulsed tooth management was mediocre, underscoring the risks associated with misleading or incomplete information in such critical situations.

2.
J Dent Sci ; 18(4): 1859-1866, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37799885

RESUMO

Abstract Background/purpose: Twin studies are crucial to assess the relative contribution of genetic and environmental factors. This study was conducted to evaluate association between deleterious oral habits and dental caries-periodontal parameters among Turkish twins. Materials and methods: The study comprised 143 pairs of dizygotic (DZ) twins and 59 pairs of monozygotic (MZ) twins aged 3-15 years. Twins were examined for dental caries, plaque index, gingival index, bleeding on probing and deleterious oral habits. Mann Whitney U test was used to examine the data. Results: The MZ twin pairs consisted of 60 male and 58 female twin pairs, whereas the DZ twin pairs consisted of 144 male and 142 female. The mean age of the twins was 9.63 ± 3.0 in MZ twins and 9.47 ± 3.2 in DZ twins. The mean DMFS value of MZ twins with bruxism is higher than those of MZ twins without bruxism (P = 0.001). The mean DMFS value of DZ twins with pacifier sucking is lower than those without (P = 0.007). A statistically significant difference was found between MZ twins with and without nail biting in terms of bleeding on probing and dmfs values (P = 0.035; P = 0.012). The mean values of the plaque index increased due to the mouth breathing in DZ twins (P = 0.024). Regarding the bleeding on probing, there was a statistically significant difference between MZ twins with and without atypical swallowing (P = 0.016). Conclusion: These findings suggest that dental caries-periodontal parameters are similarly affected by deleterious oral habits in MZ and DZ twins.

3.
Children (Basel) ; 10(4)2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37189932

RESUMO

The timing of primary tooth eruption is critical for children's health planning and the diagnosis of specific growth disorders. The purpose of this study is to assess the relationship between twin pairs' birth weight, gestational age, and gender, which are indicators of prenatal factors; breast-feeding duration, which is an indicator of postnatal factors; type of delivery, which is an indicator of maternal as well as genetic factors; and age of the primary tooth. Twin children aged from 3 to 15 years who applied to the clinic for the first dental examination constituted the sample group. In this twin study, 59 monozygotic (MZ) twin pairs and 143 dizygotic (DZ) twin pairs were included. Genetic (MZ vs. DZ), maternal (type of delivery, gestational age), perinatal (birth weight, gender), and postnatal (duration of breastfeeding) information was obtained, and effects on the children's Eruption Timing of the First Primary Tooth (ETFPT) were examined. Statistical analysis was performed using the consistent partial least squares structural equation model (robust PLSc) technique. As birth weight increased, the age at first eruption became younger, but this change was different between MZ and DZ twins (p < 0.05). While the age at first tooth eruption was older in identical twins who were breastfed for the first 6 months, this increase was not observed in DZ twins. The mean of ETFPT was calculated as 7.31 months in MZ twins and 6.75 months in DZ twins. The effect of breastfeeding and birth weight on ETFPT may differ according to zygosity in twins. MZ twins may tend to take longer to experience the eruption of their first primary teeth.

4.
J Pers Med ; 13(2)2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36836560

RESUMO

Amelogenesis imperfecta (AI) is a heterogeneous collection of hereditary enamel defects. The affected enamel can be classified as hypoplastic, hypomaturation, or hypocalcified in form. A better understanding of normal amelogenesis and improvements in our ability to diagnose AI through genetic testing can be realized through more complete knowledge of the genes and disease-causing variants that cause AI. In this study, mutational analysis was performed with whole exome sequencing (WES) to identify genetic etiology underlying the hypomaturation AI condition in affected families. Mutational analyses identified biallelic WDR72 mutations in four hypomaturation AI families. Novel mutations include a homozygous deletion and insertion mutation (NM_182758.4: c.2680_2699delinsACTATAGTT, p.(Ser894Thrfs*15)), compound heterozygous mutations (paternal c.2332dupA, p.(Met778Asnfs*4)) and (maternal c.1287_1289del, p.(Ile430del)) and a homozygous 3694 bp deletion that includes exon 14 (NG_017034.2:g.96472_100165del). A homozygous recurrent mutation variant (c.1467_1468delAT, p.(Val491Aspfs*8)) was also identified. Current ideas on WDR72 structure and function are discussed. These cases expand the mutational spectrum of WDR72 mutations causing hypomaturation AI and improve the possibility of genetic testing to accurately diagnose AI caused by WDR72 defects.

5.
Braz Oral Res ; 36: e140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36651387

RESUMO

This study evaluated the influence of socio-demographic, clinical, and parental psychological factors on oral health-related quality of life (OHRQoL) and determined their predictors in preschool-aged children with traumatic dental injury (TDI). The study sample consisted of 324 dyads of children and their parents attending the Clinics of Pediatric Dentistry at Istanbul University. After clinical examination, the Sense of Coherence (SOC), Generalized Self-Efficacy Scale, Early Childhood Oral Health Impact Scale, and Multidimensional Health Locus of Control Scale-MHLC questionnaires were administered to the parents. The statistical analyses included Spearman correlation coefficients, Mann-Whitney U tests, Kruskal-Wallis tests, multiple linear regression, and confirmatory factor analysis. Having mixed TDI, a non-nuclear family, fewer children, and weak parental SOC were important predictors of worse overall OHRQoL and its sections of child and family. Lower internal health locus of control and dental pain due to TDI were predictors of worse overall OHRQoL and child impact, respectively. Consideration of these predictors may help oral health professionals to develop prevention and treatment programs for TDI and oral health literacy programs for families.


Assuntos
Cárie Dentária , Traumatismos Dentários , Humanos , Pré-Escolar , Cárie Dentária/psicologia , Qualidade de Vida , Estudos Transversais , Saúde Bucal , Pais/psicologia , Inquéritos e Questionários
6.
Minerva Dent Oral Sci ; 72(3): 144-153, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35785933

RESUMO

BACKGROUND: This study aimed to determine the differences between preclinical and clinical dental students' knowledge, attitudes, and behaviors regarding Coronavirus disease (COVID-19). METHODS: A cross-sectional study was carried out among 303 undergraduate dental students (107 clinical students and 196 preclinical students). Questionnaires were given to the participants using an online data collection platform. The online questionnaire covered the dental students' socio-demographic information and their knowledge, attitudes and behaviors of Coronavirus disease. RESULTS: More frequently than preclinical students, clinical students benefited from the latest information about the COVID-19 outbreak obtained from television, internet news sites, and the World Health Organization website (P<0.05). The use of other protective equipment other than gloves and goggles has changed from "No" before the pandemic to "Yes" onset of the pandemic (P<0.001). The knowledge level of infection control in dentistry increased significantly more for clinical students than for preclinical students (P<0.001). CONCLUSIONS: Although dental students show reasonable knowledge, attitudes and behavior about COVID-19, attention should be taken to provide education on infectious diseases, starting from preclinical classes, and to make real information resources provided by global and national health authorities accessible to students.


Assuntos
COVID-19 , Humanos , Estudos Transversais , COVID-19/epidemiologia , SARS-CoV-2 , Estudantes de Odontologia , Conhecimentos, Atitudes e Prática em Saúde
7.
Sci Rep ; 12(1): 16477, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36183038

RESUMO

Human ACP4 (OMIM*606362) encodes a transmembrane protein that belongs to histidine acid phosphatase (ACP) family. Recessive mutations in ACP4 cause non-syndromic hypoplastic amelogenesis imperfecta (AI1J, OMIM#617297). While ACP activity has long been detected in developing teeth, its functions during tooth development and the pathogenesis of ACP4-associated AI remain largely unknown. Here, we characterized 2 AI1J families and identified a novel ACP4 disease-causing mutation: c.774_775del, p.Gly260Aspfs*29. To investigate the role of ACP4 during amelogenesis, we generated and characterized Acp4R110C mice that carry the p.(Arg110Cys) loss-of-function mutation. Mouse Acp4 expression was the strongest at secretory stage ameloblasts, and the protein localized primarily at Tomes' processes. While Acp4 heterozygous (Acp4+/R110C) mice showed no phenotypes, incisors and molars of homozygous (Acp4R110C/R110C) mice exhibited a thin layer of aplastic enamel with numerous ectopic mineralized nodules. Acp4R110C/R110C ameloblasts appeared normal initially but underwent pathology at mid-way of secretory stage. Ultrastructurally, sporadic enamel ribbons grew on mineralized dentin but failed to elongate, and aberrant needle-like crystals formed instead. Globs of organic matrix accumulated by the distal membranes of defective Tomes' processes. These results demonstrated a critical role for ACP4 in appositional growth of dental enamel probably by processing and regulating enamel matrix proteins around mineralization front apparatus.


Assuntos
Amelogênese Imperfeita , Proteínas do Esmalte Dentário , Fosfatase Ácida/metabolismo , Ameloblastos/metabolismo , Amelogênese , Amelogênese Imperfeita/metabolismo , Animais , Proteínas do Esmalte Dentário/genética , Proteínas do Esmalte Dentário/metabolismo , Histidina/metabolismo , Humanos , Camundongos , Mutação
8.
J Clin Pediatr Dent ; 46(2): 160-170, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35533222

RESUMO

BACKGROUND: The aim of this study is to investigate the relative contributions of genetic and environmental factors to variations in dental dimensions in a sample of Turkish twins, and to estimate heritability using dental casts. STUDY DESIGN: The study samples were selected from the twin children between 3-15 years old who referred for their first dental examination. Fifty nine monozygotic and one hundred and forty three dizygotic twin pairs were examined in the study. The alginate impression material used to create the plaster model of maxilla and mandible. Anterior arch width, posterior arch width, arch length and arch circumference were measured on models prepared from measurements taken for both maxilla and mandible with digital caliper. The similarities and differences of the measurements were compared between pairs of twins and zygocytes. Morever, the effects of bad oral habits, bruxism, a result of psychosocial factors on measurements were examined. Statistical analysis was performed using Paired T Test, Wilcoxon Test and Mann Whitney U test. RESULTS: A total of 404 dental models of 118 (29.2%) monozygotic and 286 (70.8%) dizygotic twins were evaluated. There was no statistical difference between sibling pairs in both monozygotic and dizygotic twins. The measurement similarity between twin siblings differed according to zygosity in all measurements (p<0.05). It has been observed that the finger sucking and mouth breathing affect the dental arch measurements (p<0.05). CONCLUSION: These results indicate that the differences in dental arch dimensions between monozygotic twin pairs are less than the difference between dizygotic twin pairs.


Assuntos
Arco Dental , Gêmeos Dizigóticos , Adolescente , Criança , Pré-Escolar , Humanos , Mandíbula , Maxila , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
9.
J Pers Med ; 12(2)2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35207639

RESUMO

Amelogenesis imperfecta (AI) is a group of rare genetic diseases affecting the tooth enamel. AI is characterized by an inadequate quantity and/or quality of tooth enamel and can be divided into three major categories: hypoplastic, hypocalcified and hypomaturation types. Even though there are some overlapping phenotypes, hypomaturation AI enamel typically has a yellow to brown discoloration with a dull appearance but a normal thickness indicating a less mineralized enamel matrix. In this study, we recruited four Turkish families with hypomaturation AI and performed mutational analysis using whole exome sequencing. These analyses revealed two novel homozygous mutations in the KLK4 gene: a nonsense mutation in exon 3 (NM_004917.4:c.170C>A, p.(Ser57*)) was found in families 1, 2 and 3 and a missense mutation in exon 6 (c.637T>C, p.(Cys213Arg)) in family 4. Functional analysis showed that the missense mutation transcript could not translate the mutant protein efficiently or generated an unstable protein that lacked functional activity. The two novel inactivating KLK4 mutations we identified caused a hypomaturation AI phenotype similar to those caused by the four previously described KLK4 nonsense and frameshift mutations. This study improves our understanding of the normal and pathologic mechanisms of enamel formation.

11.
Braz. oral res. (Online) ; 36: e140, 2022. tab
Artigo em Inglês | LILACS-Express | LILACS, BBO - Odontologia | ID: biblio-1420937

RESUMO

Abstract This study evaluated the influence of socio-demographic, clinical, and parental psychological factors on oral health-related quality of life (OHRQoL) and determined their predictors in preschool-aged children with traumatic dental injury (TDI). The study sample consisted of 324 dyads of children and their parents attending the Clinics of Pediatric Dentistry at Istanbul University. After clinical examination, the Sense of Coherence (SOC), Generalized Self-Efficacy Scale, Early Childhood Oral Health Impact Scale, and Multidimensional Health Locus of Control Scale-MHLC questionnaires were administered to the parents. The statistical analyses included Spearman correlation coefficients, Mann-Whitney U tests, Kruskal-Wallis tests, multiple linear regression, and confirmatory factor analysis. Having mixed TDI, a non-nuclear family, fewer children, and weak parental SOC were important predictors of worse overall OHRQoL and its sections of child and family. Lower internal health locus of control and dental pain due to TDI were predictors of worse overall OHRQoL and child impact, respectively. Consideration of these predictors may help oral health professionals to develop prevention and treatment programs for TDI and oral health literacy programs for families.

13.
J Clin Pediatr Dent ; 45(5): 359-370, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34740261

RESUMO

BACKGROUND: The aim of this study is to investigate the relative contributions of genetic and environmental factors to variations in dental dimensions in a sample of Turkish twins, and to estimate heritability using dental casts. STUDY DESIGN: The study samples were selected from the twin children between 3-15 years old who referred for their first dental examination. Fifty nine monozygotic and one hundred and forty three dizygotic twin pairs were examined in the study. The alginate impression material used to create the plaster model of maxilla and mandible. Anterior arch width, posterior arch width, arch length and arch circumference were measured on models prepared from measurements taken for both maxilla and mandible with digital caliper. The similarities and differences of the measurements were compared between pairs of twins and zygocytes. Morever, the effects of bad oral habits, bruxism, a result of psychosocial factors on measurements were examined. Statistical analysis was performed using Paired T Test, Wilcoxon Test and Mann Whitney U test. RESULTS: A total of 404 dental models of 118 (29.2%) monozygotic and 286 (70.8%) dizygotic twins were evaluated. There was no statistical difference between sibling pairs in both monozygotic and dizygotic twins. The measurement similarity between twin siblings differed according to zygosity in all measurements (p<0.05). It has been observed that the finger sucking and mouth breathing affect the dental arch measurements (p<0.05). CONCLUSION: These results indicate that the differences in dental arch dimensions between monozygotic twin pairs are less than the difference between dizygotic twin pairs.


Assuntos
Arco Dental , Gêmeos Dizigóticos , Adolescente , Criança , Pré-Escolar , Humanos , Mandíbula , Maxila , Gêmeos Monozigóticos
14.
Int J Oral Sci ; 13(1): 32, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593752

RESUMO

Oligodontia is the congenital absence of six or more teeth and comprises the more severe forms of tooth agenesis. Many genes have been implicated in the etiology of tooth agenesis, which is highly variable in its clinical presentation. The purpose of this study was to identify associations between genetic mutations and clinical features of oligodontia patients. An online systematic search of papers published from January 1992 to June 2021 identified 381 oligodontia cases meeting the eligibility criteria of causative gene mutation, phenotype description, and radiographic records. Additionally, ten families with oligodontia were recruited and their genetic etiologies were determined by whole-exome sequence analyses. We identified a novel mutation in WNT10A (c.99_105dup) and eight previously reported mutations in WNT10A (c.433 G > A; c.682 T > A; c.318 C > G; c.511.C > T; c.321 C > A), EDAR (c.581 C > T), and LRP6 (c.1003 C > T, c.2747 G > T). Collectively, 20 different causative genes were implicated among those 393 cases with oligodontia. For each causative gene, the mean number of missing teeth per case and the frequency of teeth missing at each position were calculated. Genotype-phenotype correlation analysis indicated that molars agenesis is more likely linked to PAX9 mutations, mandibular first premolar agenesis is least associated with PAX9 mutations. Mandibular incisors and maxillary lateral incisor agenesis are most closely linked to EDA mutations.


Assuntos
Proteínas Wnt , Humanos , Fenótipo
15.
J Pers Med ; 12(1)2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-35055328

RESUMO

Amelogenesis imperfecta (AI) is a rare genetic condition affecting the quantity and/or quality of tooth enamel. Hypomaturation AI is characterized by brownish-yellow discoloration with increased opacity and poorly mineralized enamel prone to fracture and attrition. We recruited three families affected by hypomaturation AI and performed whole exome sequencing with selected individuals in each family. Bioinformatic analysis and Sanger sequencing identified and confirmed mutations and segregation in the families. Family 1 had a novel homozygous frameshift mutation in GPR68 gene (NM_003485.3:c.78_83delinsC, p.(Val27Cysfs*146)). Family 2 had a novel homozygous nonsense mutation in SLC24A4 gene (NM_153646.4:c.613C>T, NP_705932.2:p.(Arg205*)). Family 3 also had a homozygous missense mutation in SLC24A4 gene which was reported previously (c.437C>T, p.(Ala146Val)). This report not only expands the mutational spectrum of the AI-causing genes but also improves our understanding of normal and pathologic amelogenesis.

16.
Eur J Dent ; 15(1): 145-151, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32932530

RESUMO

OBJECTIVES: This study aimed to determine the knowledge and approaches of the participants about oral and dental health. MATERIALS AND METHODS: This was a questionnaire-based cross-sectional survey. Participants' demographic characteristics, tooth brushing habits, selection of toothpaste, and reasons for visiting the dentist were examined in this study. Participants' knowledge levels of fluoride and their attitudes toward the most common fluoride applications among preventive treatments were also evaluated. Data entry and analyses were performed using SPSS statistical software. Descriptive and inferential statistics and chi-square test were used for analyzes. RESULTS: A total of 2,744 voluntary participants including 1,938 (70.6%) females and 806 (29.4%) males responded; 1,391 (50.7%) participants know the contents of their toothpaste; 1,680 (61.2%) participants point out that fluoride is effective in preventing dental caries. Female participants reported a statistically significant difference in their knowledge of what is fluoride when compared with male participants (p = 0.0001). The knowledge level of participants who had higher levels of education were statistically significantly different when compared with the participants who had lower education levels about fluoride and fluoride applications (p = 0.0001). CONCLUSIONS: The results of this study indicate that participants' attitudes toward oral health and dental care need to be improved.

17.
Sci Data ; 7(1): 348, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051450

RESUMO

There are recent studies which aimed to detect the inheritance on the etiology of dental caries exploring oral composition. We present data on the oral microbiota and its relation with dental caries and other factors in monozygotic (MZ) and dizygotic (DZ) twin children. Following clinical investigation, DNA samples were collected and isolated from saliva of 198 patients (49 MZ and 50 DZ twins) with an average age of 9.7 ± 2.7 years. Salivary bacterial microbiota analysis was performed using high throughput amplicon sequencing method targeting V3-V4 region of the 16S rRNA gene. A total of 8,297,859 raw reads corresponding to 41,908 reads per sample were obtained on average. The QIIME2-deblur workflow was used for 16S rRNA amplicon analysis. Microbiome similarity analyses between twins (based on Bray-Curtis dissimilarity, weighted and unweighted Unifrac distances) showed that monozygotic twins share more bacterial microbial content compared to dizygotic twins. This is a large microbial community dataset of MZ and DZ twins with or without dental findings which can be further used for children oral microbiome profile explorations.


Assuntos
Cárie Dentária/microbiologia , Microbiota , Boca/microbiologia , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Criança , Cárie Dentária/genética , Humanos , RNA Ribossômico 16S/genética , Saliva
18.
Acta Odontol Scand ; 78(6): 474-480, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32730719

RESUMO

OBJECTIVE: We introduced a humanoid robot for the use of techno-psychological distraction techniques in children aged 4-10 to reduce their anxiety and improve their behaviour during dental treatment. MATERIALS AND METHODS: Two hundred children (98 boys, 102 girls; mean age: 6.5 ± 1.66 years) appointed for first time for dental caries were included and randomly divided into two groups [N = 100 for each group; RG: Robot Group (accompanied by the robot), CG: Control Group (without robot accompaniment)]. Half of the children were treated under local anaesthesia (infiltration anaesthesia) (n = 50 within each group) and half of the children were treated without any local anaesthesia (n = 50 within each group) within each group. The success rate of the new robotic distraction technique was evaluated by using Parental Corah Dental Anxiety Scale, Facial Image Scale (FIS), physiological pulse rate and Frankl Behaviour Rating Scale (FBRS). RESULT: Pulse rates, which measured during treatment and after treatment, were statistically higher in CG than in RG (p < .05). After dental treatment, the FIS score was significantly higher in CG than RG (p < .05). 88.3% of the children in RG stated that they wanted the robot to be with them at the next treatment session. CONCLUSIONS: Robotic technology can successfully help in coping with dental anxiety and stress, and helps children to behave better in dental office.


Assuntos
Ansiedade ao Tratamento Odontológico , Robótica , Anestesia Local , Criança , Pré-Escolar , Cárie Dentária , Feminino , Humanos , Masculino , Procedimentos Cirúrgicos Robóticos
19.
Mol Genet Genomic Med ; 8(8): e1307, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32495503

RESUMO

BACKGROUND: Matrix metallopeptidase 20 (MMP20) is an evolutionarily conserved protease that is essential for processing enamel matrix proteins during dental enamel formation. MMP20 mutations cause human autosomal recessive pigmented hypomaturation-type amelogenesis imperfecta (AI2A2; OMIM #612529). MMP20 is expressed in both odontoblasts and ameloblasts, but its function during dentinogenesis is unclear. METHODS: We characterized 10 AI kindreds with MMP20 defects, characterized human third molars and/or Mmp20-/- mice by histology, Backscattered Scanning Electron Microscopy (bSEM), µCT, and nanohardness testing. RESULTS: We identified six novel MMP20 disease-causing mutations. Four pathogenic variants were associated with exons encoding the MMP20 hemopexin-like (PEX) domain, suggesting a necessary regulatory function. Mutant human enamel hardness was softest (13% of normal) midway between the dentinoenamel junction (DEJ) and the enamel surface. bSEM and µCT analyses of the third molars revealed reduced mineral density in both enamel and dentin. Dentin close to the DEJ showed an average hardness number 62%-69% of control. Characterization of Mmp20-/- mouse dentin revealed a significant reduction in dentin thickness and mineral density and a transient increase in predentin thickness, indicating disturbances in dentin matrix secretion and mineralization. CONCLUSION: These results expand the spectrum of MMP20 disease-causing mutations and provide the first evidence for MMP20 function during dentin formation.


Assuntos
Amelogênese Imperfeita/genética , Metaloproteinase 20 da Matriz/genética , Mutação , Alelos , Amelogênese Imperfeita/patologia , Animais , Esmalte Dentário/patologia , Dentina/patologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Linhagem
20.
Mol Genet Genomic Med ; 7(10): e00928, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31478359

RESUMO

BACKGROUND: ENAM mutations cause autosomal dominant or recessive amelogenesis imperfecta (AI) and show a dose effect: enamel malformations are more severe or only penetrant when both ENAM alleles are defective. METHODS: Whole exome sequences of recruited AI probands were initially screened for mutations in known AI candidate genes. Sanger sequencing was used to confirm sequence variations and their segregation with the disease phenotype. The co-occurrence of ENAM and LAMA3 mutations in one family raised the possibility of digenic inheritance. Enamel formed in Enam+/+ Ambn+/+ , Enam+/- , Ambn+/- , and Enam+/- Ambn+/- mice was characterized by dissection and backscattered scanning electron microscopy (bSEM). RESULTS: ENAM mutations segregating with AI in five families were identified. Two novel ENAM frameshift mutations were identified. A single-nucleotide duplication (c.395dupA/p.Pro133Alafs*13) replaced amino acids 133-1142 with a 12 amino acid (ATTKAAFEAAIT*) sequence, and a single-nucleotide deletion (c.2763delT/p.Asp921Glufs*32) replaced amino acids 921-1142 with 31 amino acids (ESSPQQASYQAKETAQRRGKAKTLLEMMCPR*). Three families were heterozygous for a previously reported single-nucleotide ENAM deletion (c.588+1delG/p.Asn197Ilefs*81). One of these families also harbored a heterozygous LAMA3 mutation (c.1559G>A/p.Cys520Tyr) that cosegregated with both the AI phenotype and the ENAM mutation. In mice, Ambn+/- maxillary incisors were normal. Ambn+/- molars were also normal, except for minor surface roughness. Ambn+/- mandibular incisors were sometimes chalky and showed minor chipping. Enam+/- incisor enamel was thinner than normal with ectopic mineral deposited laterally. Enam+/- molars were sometimes chalky and rough surfaced. Enam+/- Ambn+/- enamel was thin and rough, in part due to ectopic mineralization, but also underwent accelerated attrition. CONCLUSION: Novel ENAM mutations causing AI were identified, raising to 22 the number of ENAM variations known to cause AI. The severity of the enamel phenotype in Enam+/- Ambn+/- double heterozygous mice is caused by composite digenic effects. Digenic inheritance should be explored as a cause of AI in humans.


Assuntos
Amelogênese Imperfeita/patologia , Proteínas da Matriz Extracelular/genética , Amelogênese Imperfeita/genética , Feminino , Mutação da Fase de Leitura , Deleção de Genes , Heterozigoto , Humanos , Laminina/genética , Masculino , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Sequenciamento do Exoma
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