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Identification of potential pathogenic mutations in Chinese children with first branchial cleft anomalies detected by whole‐exome sequencing

IMPORTANCE: First branchial cleft anomalies (FBCAs) are rare congenital malformations, accounting for < 8% of all branchial cleft anomalies. However, little is currently known about the cause of FBCAs at the molecular level. OBJECTIVE: To identify genomic alterations related to the genetic etiolo...

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Autores principales: Yang, Yeran, Liu, Wei, Jin, Yaqiong, Chen, Min, Lu, Jie, Yu, Yongbo, Ren, Huimin, Han, Shujing, Chu, Ping, Guo, Yongli, Zhang, Jie, Ni, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458719/
https://www.ncbi.nlm.nih.gov/pubmed/34589676
http://dx.doi.org/10.1002/ped4.12263
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author Yang, Yeran
Liu, Wei
Jin, Yaqiong
Chen, Min
Lu, Jie
Yu, Yongbo
Ren, Huimin
Han, Shujing
Chu, Ping
Guo, Yongli
Zhang, Jie
Ni, Xin
author_facet Yang, Yeran
Liu, Wei
Jin, Yaqiong
Chen, Min
Lu, Jie
Yu, Yongbo
Ren, Huimin
Han, Shujing
Chu, Ping
Guo, Yongli
Zhang, Jie
Ni, Xin
author_sort Yang, Yeran
collection PubMed
description IMPORTANCE: First branchial cleft anomalies (FBCAs) are rare congenital malformations, accounting for < 8% of all branchial cleft anomalies. However, little is currently known about the cause of FBCAs at the molecular level. OBJECTIVE: To identify genomic alterations related to the genetic etiology of FBCAs in Chinese children. METHODS: We performed whole‐exome sequencing of samples from 10 pediatric patients with FBCAs. Data analysis was carried out using the Burrow‐Wheeler Alignment software package, and the dbSNP database for comparisons. Rare variants were further validated by Sanger sequencing. Insertion/deletions (indels) were examined using the Genome Analysis Toolkit. RESULTS: We identified 14 non‐synonymous mutations in seven potential FBCA‐susceptibility genes (TRAPPC12, NRP2, NPNT, SH3RF2, RHPN1, TENM4, and ARMCX4). We also detected 133 shared small indels in 125 genes. Gene Ontology analysis indicated that most of the identified genes played critical roles in development and differentiation pathways involved in regulating organ development. INTERPRETATION: We characterized the mutational landscape in pathways involved in development and differentiation in Chinese children with FBCA. The results identified potential pathogenic genes and mutations related to FBCA, and provide molecular‐level support for the branchial theory of FBCA pathogenesis.
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spelling pubmed-84587192021-09-28 Identification of potential pathogenic mutations in Chinese children with first branchial cleft anomalies detected by whole‐exome sequencing Yang, Yeran Liu, Wei Jin, Yaqiong Chen, Min Lu, Jie Yu, Yongbo Ren, Huimin Han, Shujing Chu, Ping Guo, Yongli Zhang, Jie Ni, Xin Pediatr Investig Original Article IMPORTANCE: First branchial cleft anomalies (FBCAs) are rare congenital malformations, accounting for < 8% of all branchial cleft anomalies. However, little is currently known about the cause of FBCAs at the molecular level. OBJECTIVE: To identify genomic alterations related to the genetic etiology of FBCAs in Chinese children. METHODS: We performed whole‐exome sequencing of samples from 10 pediatric patients with FBCAs. Data analysis was carried out using the Burrow‐Wheeler Alignment software package, and the dbSNP database for comparisons. Rare variants were further validated by Sanger sequencing. Insertion/deletions (indels) were examined using the Genome Analysis Toolkit. RESULTS: We identified 14 non‐synonymous mutations in seven potential FBCA‐susceptibility genes (TRAPPC12, NRP2, NPNT, SH3RF2, RHPN1, TENM4, and ARMCX4). We also detected 133 shared small indels in 125 genes. Gene Ontology analysis indicated that most of the identified genes played critical roles in development and differentiation pathways involved in regulating organ development. INTERPRETATION: We characterized the mutational landscape in pathways involved in development and differentiation in Chinese children with FBCA. The results identified potential pathogenic genes and mutations related to FBCA, and provide molecular‐level support for the branchial theory of FBCA pathogenesis. John Wiley and Sons Inc. 2021-06-23 /pmc/articles/PMC8458719/ /pubmed/34589676 http://dx.doi.org/10.1002/ped4.12263 Text en © 2021 Chinese Medical Association. Pediatric Investigation published by John Wiley & Sons Australia, Ltd on behalf of Futang Research Center of Pediatric Development https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Article
Yang, Yeran
Liu, Wei
Jin, Yaqiong
Chen, Min
Lu, Jie
Yu, Yongbo
Ren, Huimin
Han, Shujing
Chu, Ping
Guo, Yongli
Zhang, Jie
Ni, Xin
Identification of potential pathogenic mutations in Chinese children with first branchial cleft anomalies detected by whole‐exome sequencing
title Identification of potential pathogenic mutations in Chinese children with first branchial cleft anomalies detected by whole‐exome sequencing
title_full Identification of potential pathogenic mutations in Chinese children with first branchial cleft anomalies detected by whole‐exome sequencing
title_fullStr Identification of potential pathogenic mutations in Chinese children with first branchial cleft anomalies detected by whole‐exome sequencing
title_full_unstemmed Identification of potential pathogenic mutations in Chinese children with first branchial cleft anomalies detected by whole‐exome sequencing
title_short Identification of potential pathogenic mutations in Chinese children with first branchial cleft anomalies detected by whole‐exome sequencing
title_sort identification of potential pathogenic mutations in chinese children with first branchial cleft anomalies detected by whole‐exome sequencing
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458719/
https://www.ncbi.nlm.nih.gov/pubmed/34589676
http://dx.doi.org/10.1002/ped4.12263
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