Identification and Characterization of a Cryptic Genomic Deletion-Insertion in EYA1 Associated with Branchio-Otic Syndrome

Branchio-oto-renal spectrum disorder (BORSD) is characterized by hearing loss accompanied by ear malformations, branchial cysts, and fistulae, with (branchio-oto-renal syndrome (BORS)) or without renal abnormalities (BOS (branchio-otic syndrome)). As the most common causative gene for BORSD, dominan...

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Main Authors: Hao Zheng, Jun Xu, Yu Wang, Yun Lin, Qingqiang Hu, Xing Li, Jiusheng Chu, Changling Sun, Yongchuan Chai, Xiuhong Pang
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2021/5524381
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author Hao Zheng
Jun Xu
Yu Wang
Yun Lin
Qingqiang Hu
Xing Li
Jiusheng Chu
Changling Sun
Yongchuan Chai
Xiuhong Pang
author_facet Hao Zheng
Jun Xu
Yu Wang
Yun Lin
Qingqiang Hu
Xing Li
Jiusheng Chu
Changling Sun
Yongchuan Chai
Xiuhong Pang
author_sort Hao Zheng
collection DOAJ
description Branchio-oto-renal spectrum disorder (BORSD) is characterized by hearing loss accompanied by ear malformations, branchial cysts, and fistulae, with (branchio-oto-renal syndrome (BORS)) or without renal abnormalities (BOS (branchio-otic syndrome)). As the most common causative gene for BORSD, dominant mutations in EYA1 are responsible for approximately 40% of the cases. In a sporadic deaf patient diagnosed as BOS, we identified an apparent heterozygous genomic deletion spanning the first four coding exons and one 5′ noncoding exon of EYA1 by targeted next-generation sequencing of 406 known deafness genes. Real-time PCR at multiple regions of EYA1 confirmed the existence of this genomic deletion and extended its 5′ boundary beyond the 5′-UTR. Whole genome sequencing subsequently located the 5′ and 3′ breakpoints to 19268 bp upstream to the ATG initiation codon and 3180 bp downstream to exon 5. PCR amplification across the breakpoints in both the patient and his parents showed that the genomic alteration occurred de novo. Sanger sequencing of this PCR product revealed that it is in fact a GRCh38/hg38:chr8:g.71318554_71374171delinsTGCC genomic deletion-insertion. Our results showed that the genomic variant is responsible for the hearing loss associated with BOS and provided an example for deciphering such cryptic genomic alterations following pipelines of comprehensive exome/genome sequencing and designed verification.
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institution Kabale University
issn 2090-5904
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language English
publishDate 2021-01-01
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series Neural Plasticity
spelling doaj-art-f721e9b8a335422ea6a3bb201a7533ff2025-02-03T06:01:49ZengWileyNeural Plasticity2090-59041687-54432021-01-01202110.1155/2021/55243815524381Identification and Characterization of a Cryptic Genomic Deletion-Insertion in EYA1 Associated with Branchio-Otic SyndromeHao Zheng0Jun Xu1Yu Wang2Yun Lin3Qingqiang Hu4Xing Li5Jiusheng Chu6Changling Sun7Yongchuan Chai8Xiuhong Pang9Department of Otolaryngology-Head and Neck Surgery, Taizhou People’s Hospital, The Fifth Affiliated Hospital of Nantong University & Clinical Hospital of Dalian Medical University, Taizhou, Jiangsu, ChinaDepartment of Otolaryngology-Head and Neck Surgery, The Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Taizhou People’s Hospital, The Fifth Affiliated Hospital of Nantong University & Clinical Hospital of Dalian Medical University, Taizhou, Jiangsu, ChinaDepartment of Otolaryngology-Head and Neck Surgery, The Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Taizhou People’s Hospital, The Fifth Affiliated Hospital of Nantong University & Clinical Hospital of Dalian Medical University, Taizhou, Jiangsu, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Taizhou People’s Hospital, The Fifth Affiliated Hospital of Nantong University & Clinical Hospital of Dalian Medical University, Taizhou, Jiangsu, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Taizhou People’s Hospital, The Fifth Affiliated Hospital of Nantong University & Clinical Hospital of Dalian Medical University, Taizhou, Jiangsu, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, ChinaDepartment of Otolaryngology-Head and Neck Surgery, The Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Taizhou People’s Hospital, The Fifth Affiliated Hospital of Nantong University & Clinical Hospital of Dalian Medical University, Taizhou, Jiangsu, ChinaBranchio-oto-renal spectrum disorder (BORSD) is characterized by hearing loss accompanied by ear malformations, branchial cysts, and fistulae, with (branchio-oto-renal syndrome (BORS)) or without renal abnormalities (BOS (branchio-otic syndrome)). As the most common causative gene for BORSD, dominant mutations in EYA1 are responsible for approximately 40% of the cases. In a sporadic deaf patient diagnosed as BOS, we identified an apparent heterozygous genomic deletion spanning the first four coding exons and one 5′ noncoding exon of EYA1 by targeted next-generation sequencing of 406 known deafness genes. Real-time PCR at multiple regions of EYA1 confirmed the existence of this genomic deletion and extended its 5′ boundary beyond the 5′-UTR. Whole genome sequencing subsequently located the 5′ and 3′ breakpoints to 19268 bp upstream to the ATG initiation codon and 3180 bp downstream to exon 5. PCR amplification across the breakpoints in both the patient and his parents showed that the genomic alteration occurred de novo. Sanger sequencing of this PCR product revealed that it is in fact a GRCh38/hg38:chr8:g.71318554_71374171delinsTGCC genomic deletion-insertion. Our results showed that the genomic variant is responsible for the hearing loss associated with BOS and provided an example for deciphering such cryptic genomic alterations following pipelines of comprehensive exome/genome sequencing and designed verification.http://dx.doi.org/10.1155/2021/5524381
spellingShingle Hao Zheng
Jun Xu
Yu Wang
Yun Lin
Qingqiang Hu
Xing Li
Jiusheng Chu
Changling Sun
Yongchuan Chai
Xiuhong Pang
Identification and Characterization of a Cryptic Genomic Deletion-Insertion in EYA1 Associated with Branchio-Otic Syndrome
Neural Plasticity
title Identification and Characterization of a Cryptic Genomic Deletion-Insertion in EYA1 Associated with Branchio-Otic Syndrome
title_full Identification and Characterization of a Cryptic Genomic Deletion-Insertion in EYA1 Associated with Branchio-Otic Syndrome
title_fullStr Identification and Characterization of a Cryptic Genomic Deletion-Insertion in EYA1 Associated with Branchio-Otic Syndrome
title_full_unstemmed Identification and Characterization of a Cryptic Genomic Deletion-Insertion in EYA1 Associated with Branchio-Otic Syndrome
title_short Identification and Characterization of a Cryptic Genomic Deletion-Insertion in EYA1 Associated with Branchio-Otic Syndrome
title_sort identification and characterization of a cryptic genomic deletion insertion in eya1 associated with branchio otic syndrome
url http://dx.doi.org/10.1155/2021/5524381
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