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A Mutation in CACNA1S Is Associated with Multiple Supernumerary Cusps and Root Maldevelopment

Background: Enamel knots and Hertwig epithelial root sheath (HERS) regulate the growth and folding of the dental epithelium, which subsequently determines the final form of tooth crown and roots. We would like to investigate the genetic etiology of seven patients affected with unique clinical manife...

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Autores principales: Kantaputra, Piranit, Leelaadisorn, Niramol, Hatsadaloi, Athiwat, Quarto, Natalina, Intachai, Worrachet, Tongsima, Sissades, Kawasaki, Katsushige, Ohazama, Atsushi, Ngamphiw, Chumpol, Wiriyakijja, Paswach
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10000453/
https://www.ncbi.nlm.nih.gov/pubmed/36900039
http://dx.doi.org/10.3390/diagnostics13050895
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author Kantaputra, Piranit
Leelaadisorn, Niramol
Hatsadaloi, Athiwat
Quarto, Natalina
Intachai, Worrachet
Tongsima, Sissades
Kawasaki, Katsushige
Ohazama, Atsushi
Ngamphiw, Chumpol
Wiriyakijja, Paswach
author_facet Kantaputra, Piranit
Leelaadisorn, Niramol
Hatsadaloi, Athiwat
Quarto, Natalina
Intachai, Worrachet
Tongsima, Sissades
Kawasaki, Katsushige
Ohazama, Atsushi
Ngamphiw, Chumpol
Wiriyakijja, Paswach
author_sort Kantaputra, Piranit
collection PubMed
description Background: Enamel knots and Hertwig epithelial root sheath (HERS) regulate the growth and folding of the dental epithelium, which subsequently determines the final form of tooth crown and roots. We would like to investigate the genetic etiology of seven patients affected with unique clinical manifestations, including multiple supernumerary cusps, single prominent premolars, and single-rooted molars. Methods: Oral and radiographic examination and whole-exome or Sanger sequencing were performed in seven patients. Immunohistochemical study during early tooth development in mice was performed. Results: A heterozygous variant (c. 865A>G; p.Ile289Val) in CACNA1S was identified in all the patients, but not in an unaffected family member and control. Immunohistochemical study showed high expression of Cacna1s in the secondary enamel knot. Conclusions: This CACNA1S variant seemed to cause impaired dental epithelial folding; too much folding in the molars and less folding in the premolars; and delayed folding (invagination) of HERS, which resulted in single-rooted molars or taurodontism. Our observation suggests that the mutation in CACNA1S might disrupt calcium influx, resulting in impaired dental epithelium folding, and subsequent abnormal crown and root morphology.
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spelling pubmed-100004532023-03-11 A Mutation in CACNA1S Is Associated with Multiple Supernumerary Cusps and Root Maldevelopment Kantaputra, Piranit Leelaadisorn, Niramol Hatsadaloi, Athiwat Quarto, Natalina Intachai, Worrachet Tongsima, Sissades Kawasaki, Katsushige Ohazama, Atsushi Ngamphiw, Chumpol Wiriyakijja, Paswach Diagnostics (Basel) Case Report Background: Enamel knots and Hertwig epithelial root sheath (HERS) regulate the growth and folding of the dental epithelium, which subsequently determines the final form of tooth crown and roots. We would like to investigate the genetic etiology of seven patients affected with unique clinical manifestations, including multiple supernumerary cusps, single prominent premolars, and single-rooted molars. Methods: Oral and radiographic examination and whole-exome or Sanger sequencing were performed in seven patients. Immunohistochemical study during early tooth development in mice was performed. Results: A heterozygous variant (c. 865A>G; p.Ile289Val) in CACNA1S was identified in all the patients, but not in an unaffected family member and control. Immunohistochemical study showed high expression of Cacna1s in the secondary enamel knot. Conclusions: This CACNA1S variant seemed to cause impaired dental epithelial folding; too much folding in the molars and less folding in the premolars; and delayed folding (invagination) of HERS, which resulted in single-rooted molars or taurodontism. Our observation suggests that the mutation in CACNA1S might disrupt calcium influx, resulting in impaired dental epithelium folding, and subsequent abnormal crown and root morphology. MDPI 2023-02-27 /pmc/articles/PMC10000453/ /pubmed/36900039 http://dx.doi.org/10.3390/diagnostics13050895 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Kantaputra, Piranit
Leelaadisorn, Niramol
Hatsadaloi, Athiwat
Quarto, Natalina
Intachai, Worrachet
Tongsima, Sissades
Kawasaki, Katsushige
Ohazama, Atsushi
Ngamphiw, Chumpol
Wiriyakijja, Paswach
A Mutation in CACNA1S Is Associated with Multiple Supernumerary Cusps and Root Maldevelopment
title A Mutation in CACNA1S Is Associated with Multiple Supernumerary Cusps and Root Maldevelopment
title_full A Mutation in CACNA1S Is Associated with Multiple Supernumerary Cusps and Root Maldevelopment
title_fullStr A Mutation in CACNA1S Is Associated with Multiple Supernumerary Cusps and Root Maldevelopment
title_full_unstemmed A Mutation in CACNA1S Is Associated with Multiple Supernumerary Cusps and Root Maldevelopment
title_short A Mutation in CACNA1S Is Associated with Multiple Supernumerary Cusps and Root Maldevelopment
title_sort mutation in cacna1s is associated with multiple supernumerary cusps and root maldevelopment
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10000453/
https://www.ncbi.nlm.nih.gov/pubmed/36900039
http://dx.doi.org/10.3390/diagnostics13050895
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