Laugel-Haushalter Virginie, Morkmued Supawich, Stoetzel Corinne, Geoffroy Véronique, Muller Jean, Boland Anne, Deleuze Jean-François, Chennen Kirsley, Pitiphat Waranuch, Dollfus Hélène, Niederreither Karen, Bloch-Zupan Agnès, Pungchanchaikul Patimaporn
Laboratoire de Génétique Médicale, UMR_S INSERM U1112, IGMA, Faculté de Médecine, FMTS, Université de Strasbourg, Strasbourg, France.
Biofilm Research Group, Department of Pediatric Dentistry, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand.
Front Physiol. 2018 Sep 26;9:1329. doi: 10.3389/fphys.2018.01329. eCollection 2018.
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 (Ca1.1) (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.
在本研究中，我们报告了来自5个泰国东北部家庭的11名受影响个体所呈现的一种独特的显性遗传紊乱额外尖牙和单根表型。通过全外显子组测序（WES），我们在（Ca1.1）（NM_000069.2：c.[865A > G];[=] p.[Ile289Val];[=]）（钙通道，电压依赖性，L型，α-1s亚基，OMIM 114208）的第6外显子中鉴定出一个与该表型共分离的常见单错义突变，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。这是一个有力的遗传学证据，表明电压依赖性钙离子通道可能在影响牙齿形态发生和模式形成中发挥作用。
