Taurodontism, variations in tooth number, and misshapened crowns in Wnt10a null mice and human kindreds. Issue 1 (15th September 2014)

• Record Type: Journal Article
• Authors: Yang, Jie; Wang, Shih‐Kai; Choi, Murim; Reid, Bryan M.; Hu, Yuanyuan; Lee, Yuan‐Ling; Herzog, Curtis R.; Kim‐Berman, Hera; Lee, Moses; Benke, Paul J.; Kent Lloyd, K. C.; Simmer, James P.; Hu, Jan C.‐C.
• Is Part Of: Molecular genetics & genomic medicine. Volume 3:Issue 1(2015:Jan.)
• Page Start: 40
• Page End: 58
• Publication Date: 2014-09-15
• Subjects: Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.111
• Languages: English
• ISSNs: 2324-9269

Abstract

<abstract abstract-type="main" id="mgg3111-abs-0001"> <title>Abstract</title> <p>WNT10A is a signaling molecule involved in tooth development, and <italic>WNT10A</italic> defects are associated with tooth agenesis. We characterized <italic>Wnt10a</italic> null mice generated by the knockout mouse project (KOMP) and six families with <italic>WNT10A</italic> mutations, including a novel p.Arg104Cys defect, in the absence of <italic>EDA</italic>, <italic> EDAR</italic>, or <italic>EDARADD</italic> variations. <italic>Wnt10a</italic> null mice exhibited supernumerary mandibular fourth molars, and smaller molars with abnormal cusp patterning and root taurodontism. <italic>Wnt10a</italic><sup><italic>−/−</italic></sup> incisors showed distinctive apical–lingual wedge‐shaped defects. These findings spurred us to closely examine the dental phenotypes of our <italic>WNT10A</italic> families. <italic>WNT10A</italic> heterozygotes exhibited molar root taurodontism and mild tooth agenesis (with incomplete penetrance) in their permanent dentitions. Individuals with two defective <italic>WNT10A</italic> alleles showed severe tooth agenesis and had fewer cusps on their molars. The misshapened molar crowns and roots were consistent with the <italic>Wnt10a</italic> null phenotype and were not previously associated with <italic>WNT10A</italic> defects. The missing teeth contrasted with the presence of supplemental teeth in the <italic>Wnt10a</italic> null mice and demonstrated mammalian species differences in the roles of Wnt signaling in early tooth development. We conclude that molar crown and root dysmorphologies are caused by <italic>WNT10A</italic> defects and that the severity of the tooth agenesis correlates with the number of defective <italic>WNT10A</italic> alleles.</p> </abstract>