Genetic Evidence Supporting the Role of the Calcium Channel, CACNA1S, in Tooth Cusp and Root Patterning

Virginie Laugel-Haushalter; Supawich Morkmued; Corinne Stoetzel; Véronique Geoffroy; Jean Muller; Anne Boland; Jean-François Deleuze; Kirsley Chennen; Waranuch Pitiphat; Hélène Dollfus; Karen Niederreither; Agnès Bloch-Zupan; Patimaporn Pungchanchaikul

doi:10.3389/fphys.2018.01329

Genetic Evidence Supporting the Role of the Calcium Channel, CACNA1S, in Tooth Cusp and Root Patterning

Front Physiol. 2018 Sep 26:9:1329. doi: 10.3389/fphys.2018.01329. eCollection 2018.

Authors

Virginie Laugel-Haushalter¹, Supawich Morkmued^{2

3}, Corinne Stoetzel¹, Véronique Geoffroy¹, Jean Muller^{1

4}, Anne Boland⁵, Jean-François Deleuze⁵, Kirsley Chennen^{3

6}, Waranuch Pitiphat⁷, Hélène Dollfus^{1

8}, Karen Niederreither^{3

9}, Agnès Bloch-Zupan^{3

9

10}, Patimaporn Pungchanchaikul²

Affiliations

¹ Laboratoire de Génétique Médicale, UMR_S INSERM U1112, IGMA, Faculté de Médecine, FMTS, Université de Strasbourg, Strasbourg, France.
² Biofilm Research Group, Department of Pediatric Dentistry, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand.
³ Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CERBM, INSERM U 1258, CNRS- UMR 7104, Université de Strasbourg, Strasbourg, France.
⁴ Laboratoires de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
⁵ Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, Direction de la Recherche Fondamentale, Commissariat à l'Energie Atomique et aux Energies Alternatives, Paris, France.
⁶ Department of Computer Science, ICube, CNRS - UMR 7357, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France.
⁷ Department of Community Dentistry, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand.
⁸ Centre de Référence pour les Affections Rares en Génétique Ophtalmologique, Filière SENSGENE, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
⁹ Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
¹⁰ Hôpitaux Universitaires de Strasbourg (HUS), Pôle de Médecine et Chirurgie Bucco-Dentaires Hôpital Civil, Centre de Référence des Maladies Rares Orales et Dentaires, O-Rares, Filière Santé Maladies Rares TETE COU, European Reference Network ERN CRANIO, Strasbourg, France.

Abstract

In this study, we report a unique dominantly inherited disorganized supernumerary cusp and single root phenotype presented by 11 affected individuals belonging to 5 north-eastern Thai families. Using whole exome sequencing (WES) we identified a common single missense mutation that segregates with the phenotype in exon 6 of CACNA1S (Ca_v1.1) (NM_000069.2: c.[865A > G];[=] p.[Ile289Val];[=]), the Calcium Channel, Voltage-Dependent, L Type, Alpha-1s Subunit, OMIM ^∗ 114208), affecting a highly conserved amino-acid isoleucine residue within the pore forming subdomain of CACNA1S protein. This is a strong genetic evidence that a voltage-dependent calcium ion channel is likely to play a role in influencing tooth morphogenesis and patterning.

Keywords: NGS; calcium ion channel; dental anomalies; human; mutations; patterning; rare disease.