PMID- 28910570 OWN - NLM STAT- MEDLINE DCOM- 20190403 LR - 20190403 IS - 1544-0591 (Electronic) IS - 0022-0345 (Print) IS - 0022-0345 (Linking) VI - 97 IP - 2 DP - 2018 Feb TI - Nine Novel PAX9 Mutations and a Distinct Tooth Agenesis Genotype-Phenotype. PG - 155-162 LID - 10.1177/0022034517729322 [doi] AB - Tooth agenesis is one of the most common developmental anomalies affecting function and esthetics. The paired-domain transcription factor, Pax9, is critical for patterning and morphogenesis of tooth and taste buds. Mutations of PAX9 have been identified in patients with tooth agenesis. Despite significant progress in the genetics of tooth agenesis, many gaps in knowledge exist in refining the genotype-phenotype correlation between PAX9 and tooth agenesis. In the present study, we complete genetic and phenotypic characterization of multiplex Chinese families with nonsyndromic (NS) tooth agenesis. Direct sequencing of polymerase chain reaction products revealed 9 novel (c.140G>C, c.167T>A, c.332G>C, c.194C>A, c.271A>T, c.146delC, c.185_189dup, c.256_262dup, and c.592delG) and 2 known heterozygous mutations in the PAX9 gene among 120 probands. Subsequently, pedigrees were extended, and we confirmed that the mutations co-segregated with the tooth agenesis phenotype (with exception of families in which DNA analysis was not available). In 1 family ( n = 6), 2 individuals harbored both the PAX9 c.592delG mutation and a heterozygous missense mutation (c.739C>T) in the MSX1 gene. Clinical characterization of families segregating a PAX9 mutation reveal that all affected individuals were missing the mandibular second molar and their maxillary central incisors are most susceptible to microdontia. A significant reduction of bitter taste perception was documented in individuals harboring PAX9 mutations ( n = 3). Functional studies revealed that PAX9 haploinsufficiency or a loss of function of the PAX9 protein underlies tooth agenesis. FAU - Wong, S-W AU - Wong SW AD - 1 Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China. AD - 2 Oral and Craniofacial Biomedicine Curriculum, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. AD - 3 Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. FAU - Han, D AU - Han D AD - 1 Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China. FAU - Zhang, H AU - Zhang H AD - 4 Central Laboratory, School and Hospital of Stomatology, Peking University, Beijing, China. FAU - Liu, Y AU - Liu Y AD - 1 Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China. FAU - Zhang, X AU - Zhang X AD - 1 Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China. FAU - Miao, M Z AU - Miao MZ AD - 2 Oral and Craniofacial Biomedicine Curriculum, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. FAU - Wang, Y AU - Wang Y AD - 1 Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China. FAU - Zhao, N AU - Zhao N AD - 1 Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China. FAU - Zeng, L AU - Zeng L AD - 1 Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China. FAU - Bai, B AU - Bai B AD - 5 Department of Prosthodontics, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing, China. FAU - Wang, Y-X AU - Wang YX AD - 4 Central Laboratory, School and Hospital of Stomatology, Peking University, Beijing, China. FAU - Liu, H AU - Liu H AD - 1 Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China. AD - 6 National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China. FAU - Frazier-Bowers, S A AU - Frazier-Bowers SA AD - 7 Department of Orthodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA. FAU - Feng, H AU - Feng H AD - 1 Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing, China. AD - 6 National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China. LA - eng GR - R90 DE022527/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20170914 PL - United States TA - J Dent Res JT - Journal of dental research JID - 0354343 RN - 0 (MSX1 Transcription Factor) RN - 0 (PAX9 Transcription Factor) SB - IM MH - Adolescent MH - Adult MH - Anodontia/*genetics MH - Child MH - China MH - *DNA Mutational Analysis MH - Electrophoretic Mobility Shift Assay MH - Female MH - Fluorescent Antibody Technique MH - Genetic Association Studies MH - Humans MH - MSX1 Transcription Factor/genetics MH - Male MH - Middle Aged MH - Mutation, Missense MH - PAX9 Transcription Factor/*genetics MH - Pedigree MH - Polymerase Chain Reaction MH - Taste Disorders/genetics PMC - PMC5784472 OTO - NOTNLM OT - craniofacial anomalies OT - craniofacial genetics OT - dental agenesis OT - functional studies OT - oligodontia OT - phenotypic analysis COIS- The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. EDAT- 2017/09/15 06:00 MHDA- 2019/04/04 06:00 PMCR- 2019/02/01 CRDT- 2017/09/15 06:00 PHST- 2017/09/15 06:00 [pubmed] PHST- 2019/04/04 06:00 [medline] PHST- 2017/09/15 06:00 [entrez] PHST- 2019/02/01 00:00 [pmc-release] AID - 10.1177_0022034517729322 [pii] AID - 10.1177/0022034517729322 [doi] PST - ppublish SO - J Dent Res. 2018 Feb;97(2):155-162. doi: 10.1177/0022034517729322. Epub 2017 Sep 14.