Examination of rare genetic variants in dental enamel genes: The potential role of next-generation sequencing in primary dental care.

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Publication Date



DOI: 10.1111/ocr.12266


Objectives: To examine the potential role of next-generation sequencing (NGS) and genetic testing to guide preventive care in dental enamel disorders using publicly available databases to access the frequency of deleterious alleles in AMTN, AMLEX and ENAM, associated with amelogenesis imperfecta (AI).

Setting and sample population: Public resources, including gnomAD (The Broad Institute) and the Center for Pediatric Genomic Medicine's warehouse, which together contain variants from nearly 145 000 exomes and genomes.

Material & methods: Public resources, including sequencing data from ~145 000 exomes and genomes were queried for predicted loss of function variants with a minor allele frequency

Results: A total of 95 variants were identified in the combined dataset. If confirmed, this could be diagnostic for autosomal dominant AI.

Conclusions: The rapid integration of NGS into clinical care allows for the expansion of genetic testing for disorders that are not currently tested routinely, including non-syndromic dental enamel disorders. A genotypic-driven diagnosis of a disorder of enamel development could impact dental care, especially in young children, including early and more frequent monitoring to prevent complications. As new gene-disease associations continue to emerge, including those for common and non-syndromic craniofacial disorders, the possibility of genomic-guided precision medicine and dentistry and the development of targeted, individualized therapeutics into standard clinical care will increase substantially.

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Orthodontics & craniofacial research




Suppl 1

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MeSH Keywords

Child; Child, Preschool; Dental Care; Dental Enamel; Dental Enamel Proteins; High-Throughput Nucleotide Sequencing; Humans; Mutation


craniofacial; enamel; genetics; next-generation sequencing

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