Heterozygous Variants in <i>FREM2</i> Are Associated with Mesiodens, Supernumerary Teeth, Oral Exostoses, and Odontomas
Background: Supernumerary teeth refer to extra teeth that exceed the usual number of dentitions. A mesiodens is a particular form of supernumerary tooth, which is located in the premaxilla region. The objective of the study was to investigate the genetic etiology of extra tooth phenotypes, including...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | Diagnostics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4418/13/7/1214 |
| _version_ | 1797608187175632896 |
|---|---|
| author | Piranit Nik Kantaputra Kanich Tripuwabhrut Robert P. Anthonappa Kanoknart Chintakanon Chumpol Ngamphiw Ploy Adisornkanj Nop Porntrakulseree Bjorn Olsen Worrachet Intachai Raoul C. Hennekam Alexandre R. Vieira Sissades Tongsima |
| author_facet | Piranit Nik Kantaputra Kanich Tripuwabhrut Robert P. Anthonappa Kanoknart Chintakanon Chumpol Ngamphiw Ploy Adisornkanj Nop Porntrakulseree Bjorn Olsen Worrachet Intachai Raoul C. Hennekam Alexandre R. Vieira Sissades Tongsima |
| author_sort | Piranit Nik Kantaputra |
| collection | DOAJ |
| description | Background: Supernumerary teeth refer to extra teeth that exceed the usual number of dentitions. A mesiodens is a particular form of supernumerary tooth, which is located in the premaxilla region. The objective of the study was to investigate the genetic etiology of extra tooth phenotypes, including mesiodens and isolated supernumerary teeth. Methods: Oral and radiographic examinations and whole-exome sequencing were performed on every patient in our cohort of 122 patients, including 27 patients with isolated supernumerary teeth and 94 patients with mesiodens. A patient who had multiple supernumerary teeth also had odontomas. Results: We identified a novel (c.8498A>G; p.Asn2833Ser) and six recurrent (c.1603C>T; p.Arg535Cys, c.5852G>A; p.Arg1951His, c.6949A>T; p.Thr2317Ser; c.1549G>A; p.Val517Met, c.1921A>G; p.Thr641Ala, and c.850G>C; p.Val284Leu) heterozygous missense variants in <i>FREM2</i> in eight patients with extra tooth phenotypes. Conclusions: Biallelic variants in <i>FREM2</i> are implicated in autosomal recessive Fraser syndrome with or without dental anomalies. Here, we report for the first time that heterozygous carriers of <i>FREM2</i> variants have phenotypes including oral exostoses, mesiodens, and isolated supernumerary teeth. |
| first_indexed | 2024-03-11T05:39:54Z |
| format | Article |
| id | doaj.art-7286becf32d243d590b4794d750c4492 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-11T05:39:54Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-7286becf32d243d590b4794d750c44922023-11-17T16:29:24ZengMDPI AGDiagnostics2075-44182023-03-01137121410.3390/diagnostics13071214Heterozygous Variants in <i>FREM2</i> Are Associated with Mesiodens, Supernumerary Teeth, Oral Exostoses, and OdontomasPiranit Nik Kantaputra0Kanich Tripuwabhrut1Robert P. Anthonappa2Kanoknart Chintakanon3Chumpol Ngamphiw4Ploy Adisornkanj5Nop Porntrakulseree6Bjorn Olsen7Worrachet Intachai8Raoul C. Hennekam9Alexandre R. Vieira10Sissades Tongsima11Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, ThailandDivision of Orthodontics, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Pediatric Dentistry, University of Western Australia Dental School, Nedlands, WA 6009, AustraliaDivision of Orthodontics, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, ThailandNational Biobank of Thailand, National Science and Technology Development Agency, Khlong Luang 12120, ThailandCenter of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, ThailandDental Department, Lumphun Hospital, Lumphum 51000, ThailandDepartment of Developmental Biology, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, USACenter of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Pediatrics, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsDepartment of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USANational Biobank of Thailand, National Science and Technology Development Agency, Khlong Luang 12120, ThailandBackground: Supernumerary teeth refer to extra teeth that exceed the usual number of dentitions. A mesiodens is a particular form of supernumerary tooth, which is located in the premaxilla region. The objective of the study was to investigate the genetic etiology of extra tooth phenotypes, including mesiodens and isolated supernumerary teeth. Methods: Oral and radiographic examinations and whole-exome sequencing were performed on every patient in our cohort of 122 patients, including 27 patients with isolated supernumerary teeth and 94 patients with mesiodens. A patient who had multiple supernumerary teeth also had odontomas. Results: We identified a novel (c.8498A>G; p.Asn2833Ser) and six recurrent (c.1603C>T; p.Arg535Cys, c.5852G>A; p.Arg1951His, c.6949A>T; p.Thr2317Ser; c.1549G>A; p.Val517Met, c.1921A>G; p.Thr641Ala, and c.850G>C; p.Val284Leu) heterozygous missense variants in <i>FREM2</i> in eight patients with extra tooth phenotypes. Conclusions: Biallelic variants in <i>FREM2</i> are implicated in autosomal recessive Fraser syndrome with or without dental anomalies. Here, we report for the first time that heterozygous carriers of <i>FREM2</i> variants have phenotypes including oral exostoses, mesiodens, and isolated supernumerary teeth.https://www.mdpi.com/2075-4418/13/7/1214dental anomaliesextra teethFraser syndromesupernumerary toothtooth formationmesiodens |
| spellingShingle | Piranit Nik Kantaputra Kanich Tripuwabhrut Robert P. Anthonappa Kanoknart Chintakanon Chumpol Ngamphiw Ploy Adisornkanj Nop Porntrakulseree Bjorn Olsen Worrachet Intachai Raoul C. Hennekam Alexandre R. Vieira Sissades Tongsima Heterozygous Variants in <i>FREM2</i> Are Associated with Mesiodens, Supernumerary Teeth, Oral Exostoses, and Odontomas Diagnostics dental anomalies extra teeth Fraser syndrome supernumerary tooth tooth formation mesiodens |
| title | Heterozygous Variants in <i>FREM2</i> Are Associated with Mesiodens, Supernumerary Teeth, Oral Exostoses, and Odontomas |
| title_full | Heterozygous Variants in <i>FREM2</i> Are Associated with Mesiodens, Supernumerary Teeth, Oral Exostoses, and Odontomas |
| title_fullStr | Heterozygous Variants in <i>FREM2</i> Are Associated with Mesiodens, Supernumerary Teeth, Oral Exostoses, and Odontomas |
| title_full_unstemmed | Heterozygous Variants in <i>FREM2</i> Are Associated with Mesiodens, Supernumerary Teeth, Oral Exostoses, and Odontomas |
| title_short | Heterozygous Variants in <i>FREM2</i> Are Associated with Mesiodens, Supernumerary Teeth, Oral Exostoses, and Odontomas |
| title_sort | heterozygous variants in i frem2 i are associated with mesiodens supernumerary teeth oral exostoses and odontomas |
| topic | dental anomalies extra teeth Fraser syndrome supernumerary tooth tooth formation mesiodens |
| url | https://www.mdpi.com/2075-4418/13/7/1214 |
| work_keys_str_mv | AT piranitnikkantaputra heterozygousvariantsinifrem2iareassociatedwithmesiodenssupernumeraryteethoralexostosesandodontomas AT kanichtripuwabhrut heterozygousvariantsinifrem2iareassociatedwithmesiodenssupernumeraryteethoralexostosesandodontomas AT robertpanthonappa heterozygousvariantsinifrem2iareassociatedwithmesiodenssupernumeraryteethoralexostosesandodontomas AT kanoknartchintakanon heterozygousvariantsinifrem2iareassociatedwithmesiodenssupernumeraryteethoralexostosesandodontomas AT chumpolngamphiw heterozygousvariantsinifrem2iareassociatedwithmesiodenssupernumeraryteethoralexostosesandodontomas AT ployadisornkanj heterozygousvariantsinifrem2iareassociatedwithmesiodenssupernumeraryteethoralexostosesandodontomas AT nopporntrakulseree heterozygousvariantsinifrem2iareassociatedwithmesiodenssupernumeraryteethoralexostosesandodontomas AT bjornolsen heterozygousvariantsinifrem2iareassociatedwithmesiodenssupernumeraryteethoralexostosesandodontomas AT worrachetintachai heterozygousvariantsinifrem2iareassociatedwithmesiodenssupernumeraryteethoralexostosesandodontomas AT raoulchennekam heterozygousvariantsinifrem2iareassociatedwithmesiodenssupernumeraryteethoralexostosesandodontomas AT alexandrervieira heterozygousvariantsinifrem2iareassociatedwithmesiodenssupernumeraryteethoralexostosesandodontomas AT sissadestongsima heterozygousvariantsinifrem2iareassociatedwithmesiodenssupernumeraryteethoralexostosesandodontomas |