Genetic analysis: Wnt and other pathways in nonsyndromic tooth agenesis.

Autor: Yu M; Department of Prosthodontics, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, China., Wong SW; Oral and Craniofacial Biomedicine Curriculum, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.; Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina., Han D; Department of Prosthodontics, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, China., Cai T; National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland.
Jazyk: angličtina
Zdroj: Oral diseases [Oral Dis] 2019 Apr; Vol. 25 (3), pp. 646-651. Date of Electronic Publication: 2018 Jul 23.
DOI: 10.1111/odi.12931
Abstrakt: Tooth agenesis (TA) is one of the most common developmental anomalies that affects the number of teeth. An extensive analysis of publicly accessible databases revealed 15 causative genes responsible for nonsyndromic TA, along with their signaling pathways in Wnt/β-catenin, TGF-β/BMP, and Eda/Edar/NF-κB. However, genotype-phenotype correlation analysis showed that most of the causal genes are also responsible for syndromic TA or other conditions. In a total of 198 different mutations of the 15 genes responsible for nonsyndromic TA, 182 mutations (91.9%) are derived from seven genes (AXIN2, EDA, LRP6, MSX1, PAX9, WNT10A, and WNT10B) compared with the remaining 16 mutations (8.1%) identified in the remaining eight genes (BMP4, DKK1, EDAR, EDARADD, GREM2, KREMEN1, LTBP3, and SMOC2). Furthermore, specificity analysis in terms of the ratio of nonsyndromic TA mutations versus syndromic mutations in each of the aforementioned seven genes showed a 98.2% specificity rate in PAX9, 58.9% in WNT10A, 56.6% in MSX1, 41.2% in WNT10B, 31.4% in LRP6, 23.8% in AXIN2%, and 8.4% in EDA. These findings underscore an important role of the Wnt and Wnt-associated pathways in the genetic etiology of this heterozygous disease and shed new lights on the discovery of novel molecular mechanisms associated with tooth agenesis.
(© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)
Databáze: MEDLINE
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