Graham John M, Sanchez-Lara Pedro A, Ohazama Atsushi, Kawasaki Katsushige, Arold Stefan T, Kantaputra Piranit Nik
Department of Pediatrics, Division of Medical Genetics, Guerin Children's Hospital at Cedars-Sinai Medical Center, and David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Division of Oral Anatomy, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Int Dent J. 2025 Aug;75(4):100860. doi: 10.1016/j.identj.2025.100860. Epub 2025 Jun 23.
OBJECTIVE: Natal teeth are teeth that are present at birth. Multiple natal teeth are extremely rare. The objective of this study was to find the molecular aetiology of a unique dental phenotype including natal teeth, tooth agenesis, and root maldevelopment in a 5-generation family. METHODS: Oral and radiographic examination, linkage analysis, whole genome sequencing, and an immunohistochemical study of Kdf1 during tooth development in the mouse embryo were performed. A protein model was generated. RESULTS: We report a 5-generation family in which multiple natal teeth, oligodontia, and root maldevelopment manifested with autosomal dominant inheritance. Linkage analysis and whole genome sequencing revealed a novel pathogenic variant c.845T>G; p.Ile282Ser, which cosegregated in 9 affected and 10 unaffected family members. This amino acid Ile282 is highly conserved and is important for the stabilization of a small helical fragment. This stabilization is lost in the Ile282Ser mutant, resulting in disruption of the interaction of KDF1 with its partner proteins, including IKKA, which are important for epidermal proliferation and differentiation and subsequent tooth development. CONCLUSIONS: Our study demonstrates for the first time that natal teeth, tooth agenesis, and root maldevelopment are caused by a KDF1 variant. Our study highlights the important role of KDF1 in tooth formation and eruption.
目的：诞生牙是指出生时就已存在的牙齿。多生诞生牙极为罕见。本研究的目的是在一个五代家族中寻找一种独特牙齿表型的分子病因，该表型包括诞生牙、牙齿缺失和牙根发育异常。 方法：进行了口腔和影像学检查、连锁分析、全基因组测序以及对小鼠胚胎牙齿发育过程中Kdf1的免疫组化研究。构建了蛋白质模型。 结果：我们报告了一个五代家族，其中多生诞生牙、少牙症和牙根发育异常以常染色体显性遗传方式表现。连锁分析和全基因组测序揭示了一个新的致病变异c.845T>G；p.Ile282Ser，该变异在9名患病和10名未患病的家族成员中共同分离。氨基酸Ile282高度保守，对一个小螺旋片段的稳定很重要。在Ile282Ser突变体中这种稳定性丧失，导致KDF1与其伴侣蛋白（包括对表皮增殖、分化及后续牙齿发育很重要的IKKA）之间的相互作用被破坏。 结论：我们的研究首次证明诞生牙、牙齿缺失和牙根发育异常是由KDF1变异引起的。我们的研究突出了KDF1在牙齿形成和萌出中的重要作用。
Cochrane Database Syst Rev. 2016-8-31
Cochrane Database Syst Rev. 2018-7-31
Cochrane Database Syst Rev. 2013-4-30
Cochrane Database Syst Rev. 2022-2-11
Cochrane Database Syst Rev. 2018-5-31
Cochrane Database Syst Rev. 2017-12-28
Cochrane Database Syst Rev. 2016-10-17
Int J Paediatr Dent. 2024-7
J Am Dent Assoc. 2023-10
Biomedicines. 2023-2-7
BMJ Case Rep. 2022-11-10
Int J Mol Sci. 2022-10-18
Zotero 插件