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Mutations in WNT10B Are Identified in Individuals with Oligodontia

Tooth agenesis is one of the most common developmental anomalies in humans. Oligodontia, a severe form of tooth agenesis, is genetically and phenotypically a heterogeneous condition. Although significant efforts have been made, the genetic etiology of dental agenesis remains largely unknown. In the... Full description

Journal Title: American journal of human genetics 2016, Vol.99 (1), p.195-201
Main Author: Yu, Ping
Other Authors: Yang, Wenli , Han, Dong , Wang, Xi , Guo, Sen , Li, Jinchen , Li, Fang , Zhang, Xiaoxia , Wong, Sing-Wai , Bai, Baojing , Liu, Yao , Du, Jie , Sun, Zhong Sheng , Shi, Songtao , Feng, Hailan , Cai, Tao
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: United States: Elsevier Inc
ID: ISSN: 0002-9297
Link: https://www.ncbi.nlm.nih.gov/pubmed/27321946
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5005437
title: Mutations in WNT10B Are Identified in Individuals with Oligodontia
format: Article
creator:
  • Yu, Ping
  • Yang, Wenli
  • Han, Dong
  • Wang, Xi
  • Guo, Sen
  • Li, Jinchen
  • Li, Fang
  • Zhang, Xiaoxia
  • Wong, Sing-Wai
  • Bai, Baojing
  • Liu, Yao
  • Du, Jie
  • Sun, Zhong Sheng
  • Shi, Songtao
  • Feng, Hailan
  • Cai, Tao
subjects:
  • Anodontia - genetics
  • Asian Continental Ancestry Group - genetics
  • Base Sequence
  • China
  • Dental Pulp - pathology
  • Exome - genetics
  • Female
  • Gene mutations
  • Genetic aspects
  • Genetic Association Studies
  • Genetics
  • Genetics(clinical)
  • Health aspects
  • Hep G2 Cells
  • Heterozygote
  • Humans
  • Male
  • Mutation, Missense - genetics
  • Pedigree
  • Proto-Oncogene Proteins - genetics
  • Report
  • stomatognathic diseases
  • stomatognathic system
  • Tooth - pathology
  • Tooth diseases
  • Wnt Proteins - genetics
  • Wnt Signaling Pathway - genetics
ispartof: American journal of human genetics, 2016, Vol.99 (1), p.195-201
description: Tooth agenesis is one of the most common developmental anomalies in humans. Oligodontia, a severe form of tooth agenesis, is genetically and phenotypically a heterogeneous condition. Although significant efforts have been made, the genetic etiology of dental agenesis remains largely unknown. In the present study, we performed whole-exome sequencing to identify the causative mutations in Chinese families in whom oligodontia segregates with dominant inheritance. We detected a heterozygous missense mutation (c.632G>A [p.Arg211Gln]) in WNT10B in all affected family members. By Sanger sequencing a cohort of 145 unrelated individuals with non-syndromic oligodontia, we identified three additional mutations (c.569C>G [p.Pro190Arg], c.786G>A [p.Trp262∗], and c.851T>G [p.Phe284Cys]). Interestingly, analysis of genotype-phenotype correlations revealed that mutations in WNT10B affect the development of permanent dentition, particularly the lateral incisors. Furthermore, a functional assay demonstrated that each of these mutants could not normally enhance the canonical Wnt signaling in HEPG2 epithelial cells, in which activity of the TOPFlash luciferase reporter was measured. Notably, these mutant WNT10B ligands could not efficiently induce endothelial differentiation of dental pulp stem cells. Our findings provide the identification of autosomal-dominant WNT10B mutations in individuals with oligodontia, which increases the spectrum of congenital tooth agenesis and suggests attenuated Wnt signaling in endothelial differentiation of dental pulp stem cells.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0002-9297
fulltext: fulltext
issn:
  • 0002-9297
  • 1537-6605
url: Link


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creatorYu, Ping ; Yang, Wenli ; Han, Dong ; Wang, Xi ; Guo, Sen ; Li, Jinchen ; Li, Fang ; Zhang, Xiaoxia ; Wong, Sing-Wai ; Bai, Baojing ; Liu, Yao ; Du, Jie ; Sun, Zhong Sheng ; Shi, Songtao ; Feng, Hailan ; Cai, Tao
creatorcontribYu, Ping ; Yang, Wenli ; Han, Dong ; Wang, Xi ; Guo, Sen ; Li, Jinchen ; Li, Fang ; Zhang, Xiaoxia ; Wong, Sing-Wai ; Bai, Baojing ; Liu, Yao ; Du, Jie ; Sun, Zhong Sheng ; Shi, Songtao ; Feng, Hailan ; Cai, Tao
descriptionTooth agenesis is one of the most common developmental anomalies in humans. Oligodontia, a severe form of tooth agenesis, is genetically and phenotypically a heterogeneous condition. Although significant efforts have been made, the genetic etiology of dental agenesis remains largely unknown. In the present study, we performed whole-exome sequencing to identify the causative mutations in Chinese families in whom oligodontia segregates with dominant inheritance. We detected a heterozygous missense mutation (c.632G>A [p.Arg211Gln]) in WNT10B in all affected family members. By Sanger sequencing a cohort of 145 unrelated individuals with non-syndromic oligodontia, we identified three additional mutations (c.569C>G [p.Pro190Arg], c.786G>A [p.Trp262∗], and c.851T>G [p.Phe284Cys]). Interestingly, analysis of genotype-phenotype correlations revealed that mutations in WNT10B affect the development of permanent dentition, particularly the lateral incisors. Furthermore, a functional assay demonstrated that each of these mutants could not normally enhance the canonical Wnt signaling in HEPG2 epithelial cells, in which activity of the TOPFlash luciferase reporter was measured. Notably, these mutant WNT10B ligands could not efficiently induce endothelial differentiation of dental pulp stem cells. Our findings provide the identification of autosomal-dominant WNT10B mutations in individuals with oligodontia, which increases the spectrum of congenital tooth agenesis and suggests attenuated Wnt signaling in endothelial differentiation of dental pulp stem cells.
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subjectAnodontia - genetics ; Asian Continental Ancestry Group - genetics ; Base Sequence ; China ; Dental Pulp - pathology ; Exome - genetics ; Female ; Gene mutations ; Genetic aspects ; Genetic Association Studies ; Genetics ; Genetics(clinical) ; Health aspects ; Hep G2 Cells ; Heterozygote ; Humans ; Male ; Mutation, Missense - genetics ; Pedigree ; Proto-Oncogene Proteins - genetics ; Report ; stomatognathic diseases ; stomatognathic system ; Tooth - pathology ; Tooth diseases ; Wnt Proteins - genetics ; Wnt Signaling Pathway - genetics
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descriptionTooth agenesis is one of the most common developmental anomalies in humans. Oligodontia, a severe form of tooth agenesis, is genetically and phenotypically a heterogeneous condition. Although significant efforts have been made, the genetic etiology of dental agenesis remains largely unknown. In the present study, we performed whole-exome sequencing to identify the causative mutations in Chinese families in whom oligodontia segregates with dominant inheritance. We detected a heterozygous missense mutation (c.632G>A [p.Arg211Gln]) in WNT10B in all affected family members. By Sanger sequencing a cohort of 145 unrelated individuals with non-syndromic oligodontia, we identified three additional mutations (c.569C>G [p.Pro190Arg], c.786G>A [p.Trp262∗], and c.851T>G [p.Phe284Cys]). Interestingly, analysis of genotype-phenotype correlations revealed that mutations in WNT10B affect the development of permanent dentition, particularly the lateral incisors. Furthermore, a functional assay demonstrated that each of these mutants could not normally enhance the canonical Wnt signaling in HEPG2 epithelial cells, in which activity of the TOPFlash luciferase reporter was measured. Notably, these mutant WNT10B ligands could not efficiently induce endothelial differentiation of dental pulp stem cells. Our findings provide the identification of autosomal-dominant WNT10B mutations in individuals with oligodontia, which increases the spectrum of congenital tooth agenesis and suggests attenuated Wnt signaling in endothelial differentiation of dental pulp stem cells.
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abstractTooth agenesis is one of the most common developmental anomalies in humans. Oligodontia, a severe form of tooth agenesis, is genetically and phenotypically a heterogeneous condition. Although significant efforts have been made, the genetic etiology of dental agenesis remains largely unknown. In the present study, we performed whole-exome sequencing to identify the causative mutations in Chinese families in whom oligodontia segregates with dominant inheritance. We detected a heterozygous missense mutation (c.632G>A [p.Arg211Gln]) in WNT10B in all affected family members. By Sanger sequencing a cohort of 145 unrelated individuals with non-syndromic oligodontia, we identified three additional mutations (c.569C>G [p.Pro190Arg], c.786G>A [p.Trp262∗], and c.851T>G [p.Phe284Cys]). Interestingly, analysis of genotype-phenotype correlations revealed that mutations in WNT10B affect the development of permanent dentition, particularly the lateral incisors. Furthermore, a functional assay demonstrated that each of these mutants could not normally enhance the canonical Wnt signaling in HEPG2 epithelial cells, in which activity of the TOPFlash luciferase reporter was measured. Notably, these mutant WNT10B ligands could not efficiently induce endothelial differentiation of dental pulp stem cells. Our findings provide the identification of autosomal-dominant WNT10B mutations in individuals with oligodontia, which increases the spectrum of congenital tooth agenesis and suggests attenuated Wnt signaling in endothelial differentiation of dental pulp stem cells.
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