Chainaphaphorn Phohathai, Ngamphiw Chumpol, Tongsima Sissades, Chintakanon Kanoknart, Kawasaki Katsushige, Cox Timothy C, Ohazama Atsushi, Ketudat Cairns James R, Kantaputra Piranit Nik
Center of Excellence in Medical Genetics Research, Chiang Mai University, Chiang Mai, Thailand; Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathum Thani, Thailand.
Int Dent J. 2025 Aug 6;75(5):100928. doi: 10.1016/j.identj.2025.100928.
Kinesin Family Member 7 (KIF7) regulates ciliary integrity. Cilia-mediated sonic hedgehog signalling regulates tooth number, position, and morphology. The objective of the study was to investigate whether KIF7 variants could contribute to the formation of supernumerary teeth.
Whole-exome sequencing was performed on 153 individuals from 130 families with isolated supernumerary tooth types. Immunohistochemistry of Kif7 expression during early odontogenesis was performed in mouse embryos. Mutant KIF7 protein models were generated.
We identified 4 rare missense variants (c.160C>T;p.His54Tyr, c.175G>A;p.Val59Met, c.1964C>G;p.Pro655Arg, and c.2551C>T;p.Arg851Cys), 1 novel missense variant (c.1882 G>A;p.Glu628Lys), and 1 insertion variant (c.1893_1894insGAGGAG;p.Glu630_Glu631dup) in the KIF7 gene in patients with various orodental presentations: 5 individuals from 4 families with mesiodens, 1 proband with a supernumerary molar, and 1 proband with a compound odontoma. The p.His54Tyr and p.Val59Met variants, located in the motor domain of the KIF7 protein, are predicted to disrupt its interaction with tubulin, resulting in abnormal localisation of KIF7 in cilia. The Arg851Cys variant in the coiled-coil region and the Glu628Lys, Glu630_Glu631dup, and Pro655Arg variants in the region of unknown structure are predicted to disrupt charge balance.
This is the first report demonstrating that KIF7 variants may be contributing factors to supernumerary tooth phenotypes.
驱动蛋白家族成员7（KIF7）调节纤毛完整性。纤毛介导的音猬因子信号通路调节牙齿数量、位置和形态。本研究的目的是调查KIF7变异体是否可能导致多生牙的形成。
对来自130个孤立多生牙类型家庭的153名个体进行全外显子组测序。在小鼠胚胎中对早期牙胚发育过程中Kif7的表达进行免疫组织化学分析。构建突变KIF7蛋白模型。
我们在患有各种口腔牙齿疾病的患者的KIF7基因中鉴定出4种罕见错义变异体（c.160C>T；p.His54Tyr、c.175G>A；p.Val59Met、c.1964C>G；p.Pro655Arg和c.2551C>T；p.Arg851Cys）、1种新的错义变异体（c.1882 G>A；p.Glu628Lys）和1种插入变异体（c.1893_—1894insGAGGAG；p.Glu630_Glu631dup）：4个家庭中的5名正中多生牙患者、1名多生磨牙先证者和1名复合性牙瘤先证者。位于KIF7蛋白运动结构域的p.His54Tyr和p.Val59Met变异体预计会破坏其与微管蛋白的相互作用，导致KIF7在纤毛中的定位异常。位于卷曲螺旋区域的Arg851Cys变异体以及位于未知结构区域的Glu628Lys变异体、Glu630_Glu631dup变异体和Pro655Arg变异体预计会破坏电荷平衡。
这是第一份证明KIF7变异体可能是多生牙表型影响因素的报告。
