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 (Cav1.1) (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.
Highlights
Advances in molecular biology have increased our in-depth understanding of major processes directing tooth morphogenesis (Jernvall and Thesleff, 2012)
Patients’ medical records were scrutinized and reviewed a second time after the genotype results to search for specific phenotypes, such as myopathies, and no other existing disease was identified
We showed that Calm1, Calm2, and Calm3 were strongly expressed in all tooth types suggesting that the CACNA1S channel may play a role in calcium sensing and transport in teeth
Summary
Advances in molecular biology have increased our in-depth understanding of major processes directing tooth morphogenesis (Jernvall and Thesleff, 2012). Odontogenesis occurs in sequential developmental stages initiated with dental epithelial placode induction (seen as localized thickening of the oral ectoderm), followed by the bud, cap, and bell morphogenetic stages. Root formation and tooth eruption lead to the formation of sub-regional tooth types (incisors, canines, CACNA1S in Tooth Patterning premolars and molars), which are distinguished by a unique shape and size of both the crown and root. This regionalized layout is defined with single cusps and roots present in incisors and canines and multiple cusps and roots in molars; premolars display an intermediate crown and root pattern (2–3 cusps and single to double roots). Studies of developing mouse teeth suggest that both cusp and root initiation and patterning repeatedly re-utilize conserved developmental pathways participating in interactions between the oral ectoderm and cephalic neural crestderived ectomesenchymal cells (Thesleff and Mikkola, 2014; Balic and Thesleff, 2015)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
