Novel Mutations in GPR68 and SLC24A4 Cause Hypomaturation Amelogenesis Imperfecta

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.

Prevalence and Current Status of Dental Treatment for Amelogenesis Imperfecta and Dentinogenesis Imperfecta using National Health Insurance Database

The aim of this study was to determine the prevalence and incidence and evaluate the current status of dental treatment of Amelogenesis imperfecta (AI) and Dentinogenesis imperfecta (DI) in South Korea. The data was based on National Health Insurance Service (NHIS)-National Sample Cohort Database (2002 - 2015) and Jeonbuk National University (JBNU) Dental Hospital (2011 - 2020). The NHIS data analysis showed prevalence of AI and DI were 11.6 and 2.4 per 100,000 people, respectively. The annual incidence of AI and DI for 2013 - 2015 were 2.2 and 0.5 per 100,000. There were no statistically significant differences regarding the number of visits, the reimbursable cost among AI, DI patients and others. In the patient analysis of the JBNU dental hospital, proportion of the reimbursable and non-reimbursable cost for AI patients were 12.1% and 87.9%, while DI patients accounted for 18.6% and 81.4%.

Exploring the Pool of Pathogenic Variants of Amelogenesis Imperfecta: An Approach to the Understanding of Its Genetic Architecture

Objective: To identify which genes are associated with the clinical phenotype of amelogenesis Imperfecta (AI) and to elucidate which of these genes participate in the determination of isolated and syndromic forms.Methods: In this review, all data on mutations described in AI-related genes were obtained from HGMD® Professional. The data in relation to the mutations, inheritance, phenotype, type of AI and country were supplemented with information from the literature. The identity codes and frequency values were obtained from the dbSNP, ClinVar and OMIM databases. The percentage of specificity (PE) was determined for each gene.Results: HGMD® describes 27 genes involved in AI, which we propose to group into 5 categories: (1) genes whose mutations are associated only with isolated AI, (2) genes whose mutations cause only syndromic AI, (3) genes with both mutations that cause isolated AI and mutations responsible for other pathologies, (4) genes with mutations responsible for syndromic AI and mutations that cause other pathologies, and (5) genes with mutations that cause isolated AI and mutations that cause AI associated with syndromes and other pathologies. Using the PE calculation, the genes were ranked into 5 specificity groups. The genes of category 1 are specific for isolated AI, while the genes of categories 2 and 4 are non-specific. Interestingly, we observed that mutations in some genes were associated with different types of cancer.Conclusion: The ACP4, AMTN, MMP20, ODAPH, RELT, SLC24A4 and SP6 genes participate in causing isolated AI, and the CNNM4, DLX3 and FAM20A genes participate in causing syndromic forms of AI.

Amelogenesis imperfecta: A case series

Amelogenesis imperfecta (AI) refers to a group of rare genetic disorders that involve tooth development and that are passed down through families as a dominant trait. This condition is characterized by abnormal enamel formation caused by gene mutations that alter the quality and/or quantity of enamel. This dental problem can impact both primary and permanent dentition, varies among affected individuals, and results in esthetic and functional problems. The treatment planning for patients with AI is related to many factors, including the age of the patient, the type and severity of the disorder, intraoral conditions, and the socioeconomic status of the patient. It is crucial to plan a proper remedy, which requires collaboration among dental specialties to execute comprehensive dental treatment in order to provide a long-term solution with adequate esthetics. This clinical case study looks at three different types of amelogenesis imperfecta patients.

Functional Analysis of Rare Genetic Variants in the Negative Regulator of Intracellular Calcium Signaling RCAS/SLC10A7

The solute carrier family 10 member SLC10A7 is a negative regulator of intracellular calcium signaling (RCAS). In cell culture, SLC10A7 expression is negatively correlated with store-operated calcium entry (SOCE) via the plasma membrane. SLC10A7-deficient cells have significantly increased calcium influx after treatment with thapsigargin for depletion of ER calcium stores, whereas SLC10A7/RCAS overexpression limits calcium influx. Genetic variants in the human SLC10A7 gene are associated with skeletal dysplasia and amelogenesis imperfecta and reveal loss of function on cellular calcium influx. More recently, an additional disease-related genetic variant (P303L) as well as some novel genetic variants (V235F, T221M, I136M, L210F, P285L, and G146S) have been identified. In the present study, these variants were expressed in HEK293 cells to study their subcellular localization and their effect on cellular calcium influx. All variants were properly sorted to the ER compartment and closely co-localized with the STIM protein, a functional component of SOCE. The variants P303L and L210F showed significantly reduced effects on cellular calcium influx compared to the wild type but still maintained some degree of residual activity. This might explain the milder phenotype of patients bearing the P303L variant and might indicate disease potential for the newly identified L210F variant. In contrast, all other variants behaved like the wild type. In conclusion, the occurrence of variants in the SLC10A7 gene should be considered in patients with skeletal dysplasia and amelogenesis imperfecta. In addition to the already established variants, the present study identifies another potential disease-related SLC10A7/RCAS variant, namely, L210F, which seems to be most frequent in South Asian populations.

Multiloop edgewise archwire treatment for a patient with a severe anterior open bite and amelogenesis imperfecta

ABSTRACT Amelogenesis imperfecta is a rare hereditary disorder that affects dental enamel and is often associated with an anterior open bite. Orthodontic treatment of a 16-year-old female patient with hypocalcified amelogenesis imperfecta and a 9-mm anterior open bite was presented. Radiographic examination revealed a steep mandibular plane angle, an increased lower face height, a Class II skeletal pattern, and a convex profile. Additionally, the patient had stainless steel crowns on all upper and lower posterior teeth and composite veneers on the upper anterior teeth. The patient was treated nonsurgically using a multiloop edgewise archwire (MEAW). MEAW mechanics allowed for successful correction of the anterior open bite, with significant reduction in the mandibular plane angle and improvement in the patient's profile. No fixed retainers were used, results remained stable 78 months after removal of orthodontic appliances. MEAW mechanics should be considered for patients with large anterior open bites, although this technique requires excellent patient compliance.