Amelogenesis imperfecta: genotype-phenotype studies in 71 families.

Amelogenesis imperfecta (AI) represents hereditary conditions affecting the quality and quantity of enamel. Six genes are known to cause AI (AMELX, ENAM, MMP20, KLK4, FAM83H, and WDR72). Our aim was to determine the distribution of different gene mutations in a large AI population and evaluate phenotype-genotype relationships. Affected and unaffected family members were evaluated clinically and radiographically by one examiner. Genotyping was completed using genomic DNA obtained from blood or saliva. A total of 494 individuals were enrolled, with 430 (224 affected, 202 unaffected, and 4 not definitive) belonging to 71 families with conditions consistent with the diagnosis of AI. Diverse clinical phenotypes were observed (i.e. hypoplastic, hypocalcified, and hypomaturation). Genotyping revealed mutations in all 6 candidate genes. A molecular diagnosis was made in 132 affected individuals (59%) and in 26 of the families (37%). Mutations involved 12 families with FAM83H (46%), 6 families with AMELX (23%), 3 families with ENAM (11%), 2 families with KLK4 and MMP20 (8% for each gene), and 1 family with a WDR72 mutation (4%). Phenotypic variants were associated with allelic FAM83H and AMELX mutations. Two seemingly unrelated families had the same KLK4 mutation. Families affected with AI where candidate gene mutations were not identified could have mutations not identifiable by traditional gene sequencing (e.g. exon deletion) or they could have promoter sequence mutations not evaluated in this study. However, the results suggest that there remain new AI causative genes to be identified.

Diagnosing Developmental Defects of Enamel: Pilot Study of Online Training and Accuracy.

PURPOSE: The purpose of this study was to assess dentists' ability to correctly identify and classify development defects of enamel (DDE). METHODS: The modified DDE (MDDE) index was used to classify enamel defects into two types: (1) enamel hypoplasia-pitted, grooved, or missing enamel; or (2) enamel opacity-translucency of enamel not caused by dental caries or fluorosis (can be either demarcated or diffuse). A panel of six experts selected and scored 36 images using the MDDE, and the consensus score was used as the gold standard score in the evaluation of survey respondents. A short training table was developed to match training images to descriptors for the MDDE. A survey, including the training table, was then distributed electronically to 2,036 U.S. dentists and expanded function dental assistants from the Indian Health Service and 6,174 members of American Academy of Pediatric Dentistry. The percent of correct responses was evaluated for each image. RESULTS: Survey respondents (348 total) showed great variability in correct responses for each image, ranging from 41 to 97 percent, for each category of the MDDE. CONCLUSIONS: Enhanced training and calibration on the ability of dental providers is needed to identify the different types of development defects of enamel.

Genetic and environmental influences on dentofacial structures and oral health: studies of Australian twins and their families.

Our studies of the teeth and faces of Australian twins commenced at the School of Dentistry, The University of Adelaide in the early 1980s. There are now over 900 pairs of twins enrolled in our continuing investigations, together with 1200 relatives. There are 3 main cohorts of participants. The first cohort comprises around 300 pairs of teenage twins for whom various records have been collected, including dental casts, facial photographs, finger and palm prints and information on laterality, including handedness. The second cohort comprises around 300 pairs of twins who have been examined at 3 stages of dental development from approximately 4 years of age to about 14 years: at primary, mixed, and permanent dentition (excluding 3rd molars) stages. The most recent study of tooth emergence and oral health, for which we are currently recruiting twins, will provide a third cohort of around 500 twin pairs aged from around birth to 3 to 4 years of age. Our broad aim in these studies has been to improve our understanding of how genetic and environmental factors contribute to variation in dental and facial features, and to oral health. We have also used our data to investigate aspects of the determination of laterality, particularly the fascinating phenomenon of mirror imaging. We plan to maximize the use of the longitudinal data and DNA we have collected, and continue to collect, by performing genome-wide scans for putative genetic linkage peaks for a range of dental features, and then to test for association between a series of likely candidate genes and our phenotypes.