Whole-exome sequencing identifies a novel genotype-phenotype correlation in the entactin domain of the known deafness gene TECTA.
Postlingual progressive hearing loss, affecting primarily the high frequencies, is the clinical finding in most cases of autosomal dominant nonsyndromic hearing loss (ADNSHL). The molecular genetic etiology of ADNSHL is extremely heterogeneous. We applied whole-exome sequencing to reveal the genetic...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4016231?pdf=render |
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| author | Byung Yoon Choi Jiwoong Kim Juyong Chung Ah Reum Kim Sue Jean Mun Seong Il Kang Sang-Heon Lee Namshin Kim Seung-Ha Oh |
| author_facet | Byung Yoon Choi Jiwoong Kim Juyong Chung Ah Reum Kim Sue Jean Mun Seong Il Kang Sang-Heon Lee Namshin Kim Seung-Ha Oh |
| author_sort | Byung Yoon Choi |
| collection | DOAJ |
| description | Postlingual progressive hearing loss, affecting primarily the high frequencies, is the clinical finding in most cases of autosomal dominant nonsyndromic hearing loss (ADNSHL). The molecular genetic etiology of ADNSHL is extremely heterogeneous. We applied whole-exome sequencing to reveal the genetic etiology of high-frequency hearing loss in a mid-sized Korean family without any prior linkage data. Whole-exome sequencing of four family members (two affected and two unaffected), together with our filtering strategy based on comprehensive bioinformatics analyses, identified 21 potential pathogenic candidates. Sanger validation of an additional five family members excluded 20 variants, leaving only one novel variant, TECTA c.710C>T (p.T237I), as the strongest candidate. This variant resides in the entactin (ENT) domain and co-segregated perfectly with non-progressive high-frequency hearing loss in the family. It was absent among 700 ethnically matched control chromosomes, and the T237 residue is conserved among species, which supports its pathogenicity. Interestingly, this finding contrasted with a previously proposed genotype-phenotype correlation in which variants of the ENT domain of TECTA were associated with mid-frequency hearing loss. Based upon what we observed, we propose a novel "genotype to phenotype" correlation in the ENT domain of TECTA. Our results shed light on another important application of whole-exome sequencing: the establishment of a novel genotype-phenotype in the molecular genetic diagnosis of autosomal dominant hearing loss. |
| first_indexed | 2024-12-11T06:31:02Z |
| format | Article |
| id | doaj.art-10a69e70cdb0471ebe5ad0954c8d4057 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T06:31:02Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-10a69e70cdb0471ebe5ad0954c8d40572022-12-22T01:17:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9704010.1371/journal.pone.0097040Whole-exome sequencing identifies a novel genotype-phenotype correlation in the entactin domain of the known deafness gene TECTA.Byung Yoon ChoiJiwoong KimJuyong ChungAh Reum KimSue Jean MunSeong Il KangSang-Heon LeeNamshin KimSeung-Ha OhPostlingual progressive hearing loss, affecting primarily the high frequencies, is the clinical finding in most cases of autosomal dominant nonsyndromic hearing loss (ADNSHL). The molecular genetic etiology of ADNSHL is extremely heterogeneous. We applied whole-exome sequencing to reveal the genetic etiology of high-frequency hearing loss in a mid-sized Korean family without any prior linkage data. Whole-exome sequencing of four family members (two affected and two unaffected), together with our filtering strategy based on comprehensive bioinformatics analyses, identified 21 potential pathogenic candidates. Sanger validation of an additional five family members excluded 20 variants, leaving only one novel variant, TECTA c.710C>T (p.T237I), as the strongest candidate. This variant resides in the entactin (ENT) domain and co-segregated perfectly with non-progressive high-frequency hearing loss in the family. It was absent among 700 ethnically matched control chromosomes, and the T237 residue is conserved among species, which supports its pathogenicity. Interestingly, this finding contrasted with a previously proposed genotype-phenotype correlation in which variants of the ENT domain of TECTA were associated with mid-frequency hearing loss. Based upon what we observed, we propose a novel "genotype to phenotype" correlation in the ENT domain of TECTA. Our results shed light on another important application of whole-exome sequencing: the establishment of a novel genotype-phenotype in the molecular genetic diagnosis of autosomal dominant hearing loss.http://europepmc.org/articles/PMC4016231?pdf=render |
| spellingShingle | Byung Yoon Choi Jiwoong Kim Juyong Chung Ah Reum Kim Sue Jean Mun Seong Il Kang Sang-Heon Lee Namshin Kim Seung-Ha Oh Whole-exome sequencing identifies a novel genotype-phenotype correlation in the entactin domain of the known deafness gene TECTA. PLoS ONE |
| title | Whole-exome sequencing identifies a novel genotype-phenotype correlation in the entactin domain of the known deafness gene TECTA. |
| title_full | Whole-exome sequencing identifies a novel genotype-phenotype correlation in the entactin domain of the known deafness gene TECTA. |
| title_fullStr | Whole-exome sequencing identifies a novel genotype-phenotype correlation in the entactin domain of the known deafness gene TECTA. |
| title_full_unstemmed | Whole-exome sequencing identifies a novel genotype-phenotype correlation in the entactin domain of the known deafness gene TECTA. |
| title_short | Whole-exome sequencing identifies a novel genotype-phenotype correlation in the entactin domain of the known deafness gene TECTA. |
| title_sort | whole exome sequencing identifies a novel genotype phenotype correlation in the entactin domain of the known deafness gene tecta |
| url | http://europepmc.org/articles/PMC4016231?pdf=render |
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