Analyses of oligodontia phenotypes and genetic etiologies

Mengqi Zhou; Hong Zhang; Heather Camhi; Figen Seymen; Mine Koruyucu; Yelda Kasimoglu; Jung-Wook Kim; Hera Kim-Berman; Ninna M. R. Yuson; Paul J. Benke; Yiqun Wu; Feng Wang; Yaqin Zhu; James P. Simmer; Jan C-C. Hu

doi:10.1038/s41368-021-00135-3

International Journal of Oral Science ›› 2021, Vol. 13 ›› Issue (1) : 32 DOI: 10.1038/s41368-021-00135-3

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Analyses of oligodontia phenotypes and genetic etiologies

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¹ Dental Research Laboratory, University of Michigan School of Dentistry, Ann Arbor, MI, USA

² Department of Second Dental Center, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China

³ Department of General Dentistry, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China

⁴ Orthodontic and Pediatric Dentistry, University of Michigan School of Dentistry, 1011N. University Ave, Ann Arbor, MI, USA

⁵ Mott Children’s Health Center 806 Tuuri Place, Flint, MI, USA

⁶ Department of Pedodontics, Faculty of Dentistry, Istanbul University, Istanbul, Turkey

⁷ Department of Molecular Genetics & Dental Research Institute School of Dentistry, Seoul National University, Seoul, Korea

⁸ Department of Pediatric Dentistry & Dental Research Institute School of Dentistry, Seoul National University, Seoul, Korea

⁹ Department of Paediatric Dentistry, Women’s and Children’s Hospital, North Adelaide, SA, Australia

¹⁰ Department of Medical Genetics, Joe DiMaggio Children’s Hospital, Hollywood, FL, USA

¹¹ Department of Oral Implantology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China

^m yiqunwu@hotmail.com

^q jsimmer@umich.edu

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Abstract

Oligodontia is the congenital absence of six or more teeth and comprises the more severe forms of tooth agenesis. Many genes have been implicated in the etiology of tooth agenesis, which is highly variable in its clinical presentation. The purpose of this study was to identify associations between genetic mutations and clinical features of oligodontia patients. An online systematic search of papers published from January 1992 to June 2021 identified 381 oligodontia cases meeting the eligibility criteria of causative gene mutation, phenotype description, and radiographic records. Additionally, ten families with oligodontia were recruited and their genetic etiologies were determined by whole-exome sequence analyses. We identified a novel mutation in WNT10A (c.99_105dup) and eight previously reported mutations in WNT10A (c.433 G > A; c.682 T > A; c.318 C > G; c.511.C > T; c.321 C > A), EDAR (c.581 C > T), and LRP6 (c.1003 C > T, c.2747 G > T). Collectively, 20 different causative genes were implicated among those 393 cases with oligodontia. For each causative gene, the mean number of missing teeth per case and the frequency of teeth missing at each position were calculated. Genotype–phenotype correlation analysis indicated that molars agenesis is more likely linked to PAX9 mutations, mandibular first premolar agenesis is least associated with PAX9 mutations. Mandibular incisors and maxillary lateral incisor agenesis are most closely linked to EDA mutations.

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Mengqi Zhou, Hong Zhang, Heather Camhi, Figen Seymen, Mine Koruyucu, Yelda Kasimoglu, Jung-Wook Kim, Hera Kim-Berman, Ninna M. R. Yuson, Paul J. Benke, Yiqun Wu, Feng Wang, Yaqin Zhu, James P. Simmer, Jan C-C. Hu. Analyses of oligodontia phenotypes and genetic etiologies. International Journal of Oral Science, 2021, 13(1): 32 DOI:10.1038/s41368-021-00135-3

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