Diagnostic application of targeted resequencing for familial nonsyndromic hearing loss.
Identification of causative genes for hereditary nonsyndromic hearing loss (NSHL) is important to decide treatment modalities and to counsel the patients. Due to the genetic heterogeneity in sensorineural genetic disorders, the high-throughput method can be adapted for the efficient diagnosis. To th...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3750053?pdf=render |
| _version_ | 1818317087499616256 |
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| author | Byung Yoon Choi Gibeom Park Jungsoo Gim Ah Reum Kim Bong-Jik Kim Hyo-Sang Kim Joo Hyun Park Taesung Park Seung-Ha Oh Kyu-Hee Han Woong-Yang Park |
| author_facet | Byung Yoon Choi Gibeom Park Jungsoo Gim Ah Reum Kim Bong-Jik Kim Hyo-Sang Kim Joo Hyun Park Taesung Park Seung-Ha Oh Kyu-Hee Han Woong-Yang Park |
| author_sort | Byung Yoon Choi |
| collection | DOAJ |
| description | Identification of causative genes for hereditary nonsyndromic hearing loss (NSHL) is important to decide treatment modalities and to counsel the patients. Due to the genetic heterogeneity in sensorineural genetic disorders, the high-throughput method can be adapted for the efficient diagnosis. To this end, we designed a new diagnostic pipeline to screen all the reported candidate genes for NSHL. For validation of the diagnostic pipeline, we focused upon familial NSHL cases that are most likely to be genetic, rather than to be infectious or environmental. Among the 32 familial NSHL cases, we were able to make a molecular genetic diagnosis from 12 probands (37.5%) in the first stage by their clinical features, characteristic inheritance pattern and further candidate gene sequencing of GJB2, SLC26A4, POU3F4 or mitochondrial DNA. Next we applied targeted resequencing on 80 NSHL genes in the remaining 20 probands. Each proband carried 4.8 variants that were not synonymous and had the occurring frequency of less than three among the 20 probands. These variants were then filtered out with the inheritance pattern of the family, allele frequency in normal hearing 80 control subjects, clinical features. Finally NSHL-causing candidate mutations were identified in 13(65%) of the 20 probands of multiplex families, bringing the total solve rate (or detection rate) in our familial cases to be 78.1% (25/32) Damaging mutations discovered by the targeted resequencing were distributed in nine genes such as WFS1, COCH, EYA4, MYO6, GJB3, COL11A2, OTOF, STRC and MYO3A, most of which were private. Despite the advent of whole genome and whole exome sequencing, we propose targeted resequencing and filtering strategy as a screening and diagnostic tool at least for familial NSHL to find mutations based upon its efficacy and cost-effectiveness. |
| first_indexed | 2024-12-13T09:31:45Z |
| format | Article |
| id | doaj.art-a480baa44e50448da7ebfd8935403185 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T09:31:45Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a480baa44e50448da7ebfd89354031852022-12-21T23:52:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e6869210.1371/journal.pone.0068692Diagnostic application of targeted resequencing for familial nonsyndromic hearing loss.Byung Yoon ChoiGibeom ParkJungsoo GimAh Reum KimBong-Jik KimHyo-Sang KimJoo Hyun ParkTaesung ParkSeung-Ha OhKyu-Hee HanWoong-Yang ParkIdentification of causative genes for hereditary nonsyndromic hearing loss (NSHL) is important to decide treatment modalities and to counsel the patients. Due to the genetic heterogeneity in sensorineural genetic disorders, the high-throughput method can be adapted for the efficient diagnosis. To this end, we designed a new diagnostic pipeline to screen all the reported candidate genes for NSHL. For validation of the diagnostic pipeline, we focused upon familial NSHL cases that are most likely to be genetic, rather than to be infectious or environmental. Among the 32 familial NSHL cases, we were able to make a molecular genetic diagnosis from 12 probands (37.5%) in the first stage by their clinical features, characteristic inheritance pattern and further candidate gene sequencing of GJB2, SLC26A4, POU3F4 or mitochondrial DNA. Next we applied targeted resequencing on 80 NSHL genes in the remaining 20 probands. Each proband carried 4.8 variants that were not synonymous and had the occurring frequency of less than three among the 20 probands. These variants were then filtered out with the inheritance pattern of the family, allele frequency in normal hearing 80 control subjects, clinical features. Finally NSHL-causing candidate mutations were identified in 13(65%) of the 20 probands of multiplex families, bringing the total solve rate (or detection rate) in our familial cases to be 78.1% (25/32) Damaging mutations discovered by the targeted resequencing were distributed in nine genes such as WFS1, COCH, EYA4, MYO6, GJB3, COL11A2, OTOF, STRC and MYO3A, most of which were private. Despite the advent of whole genome and whole exome sequencing, we propose targeted resequencing and filtering strategy as a screening and diagnostic tool at least for familial NSHL to find mutations based upon its efficacy and cost-effectiveness.http://europepmc.org/articles/PMC3750053?pdf=render |
| spellingShingle | Byung Yoon Choi Gibeom Park Jungsoo Gim Ah Reum Kim Bong-Jik Kim Hyo-Sang Kim Joo Hyun Park Taesung Park Seung-Ha Oh Kyu-Hee Han Woong-Yang Park Diagnostic application of targeted resequencing for familial nonsyndromic hearing loss. PLoS ONE |
| title | Diagnostic application of targeted resequencing for familial nonsyndromic hearing loss. |
| title_full | Diagnostic application of targeted resequencing for familial nonsyndromic hearing loss. |
| title_fullStr | Diagnostic application of targeted resequencing for familial nonsyndromic hearing loss. |
| title_full_unstemmed | Diagnostic application of targeted resequencing for familial nonsyndromic hearing loss. |
| title_short | Diagnostic application of targeted resequencing for familial nonsyndromic hearing loss. |
| title_sort | diagnostic application of targeted resequencing for familial nonsyndromic hearing loss |
| url | http://europepmc.org/articles/PMC3750053?pdf=render |
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