Endo-periodontal lesions (EPLs) involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms,including unique anatomical and microbiological characteristics and multiple cont...Endo-periodontal lesions (EPLs) involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms,including unique anatomical and microbiological characteristics and multiple contributing factors.This etiological complexity leads to difficulties in determining patient prognosis,posing great challenges in clinical practice.Furthermore,EPL-affected teeth require multidisciplinary therapy,including periodontal therapy,endodontic therapy and others,but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy.By compiling the most recent findings on the etiology,pathogenesis,clinical characteristics,diagnosis,therapy,and prognosis of EPL-affected teeth,this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.展开更多
Objective:He-Zhao deficiency was originally described as a severe type of nonsyndromic hypodontia,and the causative gene locus was mapped to chromosome 10q11.2.The aim of this study was to identify potential genetic m...Objective:He-Zhao deficiency was originally described as a severe type of nonsyndromic hypodontia,and the causative gene locus was mapped to chromosome 10q11.2.The aim of this study was to identify potential genetic mutations that could cause He-Zhao deficiency.Methods:Patients with He-Zhao deficiency and their unaffected relatives of the large pedigree were investigated.The whole-exome sequencing using next-generation sequencing was employed to identify genetic variants.The data generated from the whole-exome sequencing using the Illumina Novaseq 6000 system were further analyzed by Burrows-Wheeler Aligner software,Sequence Alignment/Map tools and ANNOVAR tool.In vitro luciferase assay was used to investigate the effect of the detected mutation on gene expression.R environment was used to conduct t-tests.The study protocol was approved by the Research Ethics Committee of Bio-X Institutes,Shanghai Jiao Tong University(M2011004).Results:The exomes of five patients with He-Zhao deficiency and two of their unaffected relatives identified a mutation in PRKG1αas the molecular etiology of the disease.The variant c.-144 C>A of PRKG1 isoform 1 cosegregated with permanent tooth agenesis in 93 family members who were older than 12,at which time the primary teeth should have been replaced with permanent teeth.Functional studies suggested that the mutant allele promotes gene transcription by increasing its promoter activity.Conclusion:c.-144 C>A variant of PRKG1αinvolving odontoclast-associated root resorption is responsible for He-Zhao deficiency,unlike other forms of hypodontia,which typically involve odontoblast dysfunction.展开更多
基金supported by Jiangsu Province Key Research and Development Program(No.BE2022670)the National Key Research and Development Program of China(No.2023YFC2506300)+1 种基金Jiangsu Provincial Medical Key Discipline Cultivation Unit(No.JSDW202246)Nanjing Medical Science and Technology development Fund(ZKX22054).
文摘Endo-periodontal lesions (EPLs) involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms,including unique anatomical and microbiological characteristics and multiple contributing factors.This etiological complexity leads to difficulties in determining patient prognosis,posing great challenges in clinical practice.Furthermore,EPL-affected teeth require multidisciplinary therapy,including periodontal therapy,endodontic therapy and others,but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy.By compiling the most recent findings on the etiology,pathogenesis,clinical characteristics,diagnosis,therapy,and prognosis of EPL-affected teeth,this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.
基金National Natural Science Foundation of China(Nos.81971254 and 81771440)Shanghai Municipal Science and Technology Major Project(No.2017SHZDZX01).
文摘Objective:He-Zhao deficiency was originally described as a severe type of nonsyndromic hypodontia,and the causative gene locus was mapped to chromosome 10q11.2.The aim of this study was to identify potential genetic mutations that could cause He-Zhao deficiency.Methods:Patients with He-Zhao deficiency and their unaffected relatives of the large pedigree were investigated.The whole-exome sequencing using next-generation sequencing was employed to identify genetic variants.The data generated from the whole-exome sequencing using the Illumina Novaseq 6000 system were further analyzed by Burrows-Wheeler Aligner software,Sequence Alignment/Map tools and ANNOVAR tool.In vitro luciferase assay was used to investigate the effect of the detected mutation on gene expression.R environment was used to conduct t-tests.The study protocol was approved by the Research Ethics Committee of Bio-X Institutes,Shanghai Jiao Tong University(M2011004).Results:The exomes of five patients with He-Zhao deficiency and two of their unaffected relatives identified a mutation in PRKG1αas the molecular etiology of the disease.The variant c.-144 C>A of PRKG1 isoform 1 cosegregated with permanent tooth agenesis in 93 family members who were older than 12,at which time the primary teeth should have been replaced with permanent teeth.Functional studies suggested that the mutant allele promotes gene transcription by increasing its promoter activity.Conclusion:c.-144 C>A variant of PRKG1αinvolving odontoclast-associated root resorption is responsible for He-Zhao deficiency,unlike other forms of hypodontia,which typically involve odontoblast dysfunction.