Deep dental phenotyping and a novel FAM20A variant in patients with amelogenesis imperfecta type IG
Kanokwan Sriwattanapong
Center of Excellence in Genomics and Precision Dentistry, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Contribution: Formal analysis, Investigation, Writing - original draft, Writing - review & editing
Search for more papers by this authorThanakorn Theerapanon
Center of Excellence in Genomics and Precision Dentistry, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Contribution: Formal analysis, Writing - review & editing
Search for more papers by this authorChompak Khamwachirapitak
Center of Excellence in Genomics and Precision Dentistry, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Contribution: Investigation, Writing - review & editing
Search for more papers by this authorPannagorn Sae-ear
Oral Biology Research Center, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Contribution: Formal analysis, Writing - review & editing
Search for more papers by this authorAnucharte Srijunbarl
Dental Materials R&D Center, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Contribution: Investigation, Writing - review & editing
Search for more papers by this authorCorresponding Author
Thantrira Porntaveetus
Center of Excellence in Genomics and Precision Dentistry, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Correspondence
Thantrira Porntaveetus, Center of Excellence in Genomics and Precision Dentistry, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
Email: [email protected]
Search for more papers by this authorVorasuk Shotelersuk
Center of Excellence for Medical Genomics, Medical Genomics Cluster, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
Search for more papers by this authorKanokwan Sriwattanapong
Center of Excellence in Genomics and Precision Dentistry, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Contribution: Formal analysis, Investigation, Writing - original draft, Writing - review & editing
Search for more papers by this authorThanakorn Theerapanon
Center of Excellence in Genomics and Precision Dentistry, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Contribution: Formal analysis, Writing - review & editing
Search for more papers by this authorChompak Khamwachirapitak
Center of Excellence in Genomics and Precision Dentistry, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Contribution: Investigation, Writing - review & editing
Search for more papers by this authorPannagorn Sae-ear
Oral Biology Research Center, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Contribution: Formal analysis, Writing - review & editing
Search for more papers by this authorAnucharte Srijunbarl
Dental Materials R&D Center, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Contribution: Investigation, Writing - review & editing
Search for more papers by this authorCorresponding Author
Thantrira Porntaveetus
Center of Excellence in Genomics and Precision Dentistry, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Correspondence
Thantrira Porntaveetus, Center of Excellence in Genomics and Precision Dentistry, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
Email: [email protected]
Search for more papers by this authorVorasuk Shotelersuk
Center of Excellence for Medical Genomics, Medical Genomics Cluster, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
Search for more papers by this authorAbstract
Objectives
To identify etiologic variants and perform deep dental phenotyping in patients with amelogenesis imperfecta (AI).
Methods
Three patients of two unrelated families were evaluated. Genetic variants were investigated by exome and Sanger sequencing. An unerupted permanent third molar (AI1) from Patient1 and a deciduous first molar (AI2) from Patient2, along with three tooth-type matched controls for each were characterized.
Results
All three patients harbored biallelic pathogenic variants in FAM20A, indicating AI1G. Of the four identified variants, one, c.1231C > T p.(Arg411Trp), was novel. Patient1 possessed the largest deletion, 7531 bp, ever identified in FAM20A. In addition to hypoplastic enamel, multiple impacted teeth, intrapulpal calcification, pericoronal radiolucencies, malocclusion, and periodontal infections were found in all three patients, gingival hyperplasia in Patient1 and Patient2, and alveolar bone exostosis in Patient3. Surface roughness was increased in AI1 but decreased in AI2. Decreased enamel mineral density, hardness, and elastic modulus were observed in AI1 enamel and dentin and AI2 dentin, along with decreased phosphorus, increased carbon, and increased calcium/phosphorus and carbon/oxygen ratios. Severely collapsed enamel rods and disorganized dentin–enamel junction were observed.
Conclusions
We report a novel FAM20A variant and, for the first time, the defective mineral composition and physical/mechanical properties of AI1G teeth.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The datasets generated and/or analysed during the current study are available in the ClinVar archive. The accession numbers are as follows: SCV002526662: c.758A>G p.(Tyr253Cys); SCV002525504: c.1109+3_1109+7delinsTGGTC; SCV002525505: c.1231C>T p.Arg411Trp; SCV002526663: NC_000017.10: g.66530406_66537936del.
Supporting Information
| Filename | Description |
|---|---|
| odi14510-sup-0001-Supinfo.docxWord 2007 document , 3.1 MB |
Appendix S1 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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