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Study Description

The long-term objective of this research project is to discover the complete spectrum of genes that contribute to the etiologies of genetic disorders of the dentition. Inherited tooth defects can be isolated (the only symptom) or syndromic (having additional symptoms) and can be caused by mutations in many different genes. Clinically, it can be difficult to distinguish among the diverse forms. Making an accurate diagnosis would be greatly improved if reliable tests could identify the specific genetic defect that causes the disease in each case. Current technology can identify the numerous sequence variations throughout a patient's exome, but the disease-causing variation among them cannot be identified unless it is already on the list of genes that potentially cause the disease.

A diagnosis based upon the genetic defect that causes the disorder distinguishes between isolated and syndromic tooth defects. A precise diagnosis permits formulation of a more accurate prognosis, which informs treatment decisions. The benefits of accomplishing our aims are to 1) enable genetic testing to achieve a precise and accurate diagnosis, and thereby optimize treatment, and 2) improve our understanding of normal and pathological tooth formation, leading to future improvements in treatment and eventually cures.

Our short-term objectives are to 1) recruit kindreds with inherited disorders affecting their dentition, characterize their dental phenotype (and non-dental phenotypes when applicable) and the distribution of the disorder throughout the family, and 2) determine the genetic etiology of their disorders.

  • Study Types: Parent-Offspring Trios, Case-Control
  • Number of study subjects that have individual level data available through Authorized Access: 100

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

Inclusion criteria All kindreds with appropriate hereditary conditions (amelogenesis imperfecta, dentinogenesis imperfect, dentin dysplasia, oligodontia, supernumerary teeth, etc.) involving the dentition will be recruited regardless of their race, gender or age, and available family members of each kindred will be invited to join.

Exclusion criteria Individuals with dental defects resulted from environmental factors such as illness, nutritional disturbances, and/or medications.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Exome Sequencing Illumina HiSeq 2500 N/A N/A
Study History

Our lab has devoted significant effort in determining the genetic etiologies of commonly encountered inherited dental defects affecting tooth structure, shape, number and eruption. To date, we have identified amelogenesis imperfecta-causing mutations in 38 amelogenesis imperfecta (AI) kindreds, including the first reported mutations in MMP20 (GeneID: 9313, Kim et al., 2005 PMID:15744043), FAM83H (GeneID:286077, Kim et al., 2008 PMID:18252228), and ITGB6 (GeneID:3694, Wang et al., 2014 PMID: 24305999) causing AI and FAM20A (GeneID:54757, Wang et al., 2013 PMID:23468644) mutations causing enamel renal syndrome. The characterization of ~40 novel disease-causing mutations in 15 different genes: ALPL (GeneID:249), AMELX (GeneID:265), COL1A2 (GeneID:1278), DSPP (GeneID:1834), ENAM (GeneID:10117), FAM20A (GeneID:54757), FAM83H (GeneID:286077), KLK4 (GeneID:9622), LAMB3 (GeneID:3914), MMP20 (GeneID:9313), MSX1 (GeneID:4487) , PAX9 (GeneID:5083), SLC24A4 (GeneID:123041), STIM1 (GeneID:6786), and WDR72 (GeneID:256764) have advanced our understanding of tooth development and pathologic mechanisms of many inherited dental defects.

Selected publications
Diseases/Traits Related to Study (MESH terms)
Links to Related Resources
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Study Attribution