A Mutation in CACNA1S Is Associated with Multiple Supernumerary Cusps and Root Maldevelopment.
A Mutation in CACNA1S Is Associated with Multiple Supernumerary Cusps and Root Maldevelopment.
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DOI：
10.3390/diagnostics13050895
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发表时间：
2023-02-27
期刊：
影响因子：
3.6
通讯作者：
Wiriyakijja, Paswach
中科院分区：
文献类型：
--
作者：
Kantaputra, Piranit;Leelaadisorn, Niramol;Hatsadaloi, Athiwat;Quarto, Natalina;Intachai, Worrachet;Tongsima, Sissades;Kawasaki, Katsushige;Ohazama, Atsushi;Ngamphiw, Chumpol;Wiriyakijja, Paswach
关键词：
背景：牙釉质结和Hertwig上皮根鞘（Hertwig epithelial root sheath， HERS）调节牙上皮的生长和折叠，从而决定牙冠和牙根的最终形态。我们希望研究7例具有独特临床表现的患者的遗传病因，包括多个多尖牙，单个突出的前磨牙和单根磨牙。方法：对7例患者进行口腔和放射学检查以及全外显子组或Sanger测序。对小鼠早期牙齿发育过程进行免疫组化研究。结果：在所有患者中发现了CACNA1S的杂合变异（c. 865A >g; p.Ile289Val），但在未受影响的家庭成员和对照中未发现。免疫组化研究显示Cacna1s在继发性牙釉质结中高表达。结论：CACNA1S变异可能导致牙上皮折叠受损；磨牙折叠过多，前磨牙折叠较少；延迟折叠（内陷），导致单根磨牙或紧牙症。我们的观察表明，CACNA1S的突变可能会破坏钙的内流，导致牙上皮折叠受损，进而导致冠和根形态异常。
Background: Enamel knots and Hertwig epithelial root sheath (HERS) regulate the growth and folding of the dental epithelium, which subsequently determines the final form of tooth crown and roots. We would like to investigate the genetic etiology of seven patients affected with unique clinical manifestations, including multiple supernumerary cusps, single prominent premolars, and single-rooted molars. Methods: Oral and radiographic examination and whole-exome or Sanger sequencing were performed in seven patients. Immunohistochemical study during early tooth development in mice was performed. Results: A heterozygous variant (c. 865A>G; p.Ile289Val) in CACNA1S was identified in all the patients, but not in an unaffected family member and control. Immunohistochemical study showed high expression of Cacna1s in the secondary enamel knot. Conclusions: This CACNA1S variant seemed to cause impaired dental epithelial folding; too much folding in the molars and less folding in the premolars; and delayed folding (invagination) of HERS, which resulted in single-rooted molars or taurodontism. Our observation suggests that the mutation in CACNA1S might disrupt calcium influx, resulting in impaired dental epithelium folding, and subsequent abnormal crown and root morphology.
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影响因子：
14.9
作者：
Zhang, Han;Gong, Xuyan;Xu, Xiaoqiao;Wang, Xiaogang;Sun, Yao
通讯作者：
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影响因子：
2.1
作者：
Brook, A. H.;Jernvall, J.;Townsend, G. C.
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作者：
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DOI：
10.1073/pnas.2008850118
发表时间：
2021-01-05
影响因子：
11.1
作者：
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通讯作者：
Silcox, Mary T.
影响因子：
64.8
作者：
Harjunmaa, Enni;Kallonen, Aki;Jernvall, Jukka
通讯作者：
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