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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Wiley
2021-01-01
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| 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. |
| format | Article |
| id | doaj-art-f721e9b8a335422ea6a3bb201a7533ff |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| 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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