Genetic Variants in Protein Tyrosine Phosphatase Non-Receptor Type 23 Are Responsible for Mesiodens Formation.

Autor: Adisornkanj P; Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand.; Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand., Chanprasit R; Dental Department, Wiang Kaen Hospital, Wiang Kaen, Chiang Rai 57310, Thailand., Eliason S; Department of Anatomy and Cell Biology and the Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA 52242, USA., Fons JM; Centre for Craniofacial and Regenerative Biology, King's College London, Floor 27 Guy' Hospital, London Bridge, London SE1 9RT, UK., Intachai W; Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand., Tongsima S; National Biobank of Thailand, National Science and Technology Development Agency, Thailand Science Park, Pathum Thani 12120, Thailand., Olsen B; Department of Developmental Biology, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, USA., Arold ST; Computational Bioscience Research Center, Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.; Center for Structural Biology, National Institute of Health and Medical Research, National Centre for Scientific Research, University of Montpellier, 34090 Montpellier, France., Ngamphiw C; National Biobank of Thailand, National Science and Technology Development Agency, Thailand Science Park, Pathum Thani 12120, Thailand., Amendt BA; Department of Anatomy and Cell Biology and the Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA 52242, USA.; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA 52242, USA., Tucker AS; Centre for Craniofacial and Regenerative Biology, King's College London, Floor 27 Guy' Hospital, London Bridge, London SE1 9RT, UK., Kantaputra P; Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand.; Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand.
Jazyk: angličtina
Zdroj: Biology [Biology (Basel)] 2023 Mar 01; Vol. 12 (3). Date of Electronic Publication: 2023 Mar 01.
DOI: 10.3390/biology12030393
Abstrakt: A mesiodens is a supernumerary tooth located in the midline of the premaxilla. To investigate the genetic cause of mesiodens, clinical and radiographic examination were performed on 23 family members of a two-generation Hmong family. Whole exome sequencing (WES) or Sanger sequencing were performed in 22 family members and two unrelated Thai patients with mesiodens. WES in the Hmong family revealed a missense mutation (c.1807G>A;p.Glu603Lys) in PTPN23 in seven affected members and six unaffected members. The mode of inheritance was autosomal dominance with incomplete penetrance (53.84%). Two additional mutations in PTPN23 , c.2248C>G;p.Pro750Ala and c.3298C>T;p.Arg1100Cys were identified in two unrelated patients with mesiodens. PTPN23 is a regulator of endosomal trafficking functioning to move activated membrane receptors, such as EGFR, from the endosomal sorting complex towards the ESCRT-III complex for multivesicular body biogenesis, lysosomal degradation, and subsequent downregulation of receptor signaling. Immunohistochemical study and RNAscope on developing mouse embryos showed broad expression of PTPN23 in oral tissues, while immunofluorescence showed that EGFR was specifically concentrated in the midline epithelium. Importantly, PTPN23 mutant protein was shown to have reduced phosphatase activity. In conclusion, mesiodens were associated with genetic variants in PTPN23 , suggesting that mesiodens may form due to defects in endosomal trafficking, leading to disrupted midline signaling.
Databáze: MEDLINE
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