Table_5_Genetic Evidence Supporting the Role of the Calcium Channel, CACNA1S, in Tooth Cusp and Root Patterning.xlsx

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.

本研究报道了一种独特的显性遗传性紊乱型额外牙尖与单根表型，该表型见于泰国东北部5个家族的11名受累个体。本研究采用全外显子组测序（whole exome sequencing, WES），在CACNA1S（又称Cav1.1，钙通道电压依赖性L型α1s亚基，OMIM *114208）的第6外显子中鉴定出一种与该表型共分离的常见单碱基错义突变，其变异位点为NM_000069.2: c.[865A>G];[=]，对应的蛋白产物改变为p.[Ile289Val];[=]，该突变影响了CACNA1S蛋白孔形成亚结构域内一个高度保守的异亮氨酸残基。本研究为电压依赖性钙离子通道可能参与牙齿形态发生与模式形成提供了强有力的遗传学证据。