Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next‐generation sequencing of the SLC26A4 gene
Abstract Background The enlarged vestibular aqueduct (EVA) is the commonest malformation of inner ear accompanied by sensorineural hearing loss in children. Three genes SLC26A4, FOXI1, and KCNJ10 have been associated with EVA, among them SLC26A4 being the most common. Yet, hotspot mutation screening...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-08-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1734 |
| _version_ | 1818733991278149632 |
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| author | Yongan Tian Hongen Xu Danhua Liu Juanli Zhang Zengguang Yang Sen Zhang Huanfei Liu Ruijun Li Yingtao Tian Beiping Zeng Tong Li Qianyu Lin Haili Wang Xiaohua Li Wei Lu Ying Shi Yan Zhang Hui Zhang Chang Jiang Ying Xu Bei Chen Jun Liu Wenxue Tang |
| author_facet | Yongan Tian Hongen Xu Danhua Liu Juanli Zhang Zengguang Yang Sen Zhang Huanfei Liu Ruijun Li Yingtao Tian Beiping Zeng Tong Li Qianyu Lin Haili Wang Xiaohua Li Wei Lu Ying Shi Yan Zhang Hui Zhang Chang Jiang Ying Xu Bei Chen Jun Liu Wenxue Tang |
| author_sort | Yongan Tian |
| collection | DOAJ |
| description | Abstract Background The enlarged vestibular aqueduct (EVA) is the commonest malformation of inner ear accompanied by sensorineural hearing loss in children. Three genes SLC26A4, FOXI1, and KCNJ10 have been associated with EVA, among them SLC26A4 being the most common. Yet, hotspot mutation screening can only diagnose a small number of patients. Methods Thus, in this study, we designed a new molecular diagnosis panel for EVA based on multiplex PCR enrichment and next‐generation sequencing of the exon and flanking regions of SLC26A4. A total of 112 hearing loss families with EVA were enrolled and the pathogenicity of the rare variants detected was interpreted according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Results Our results showed that 107/112 (95.54%) families carried SLC26A4 biallelic mutations, 4/112 (3.57%) carried monoallelic variants, and 1/112 (0.89%) had none variant, resulting in a diagnostic rate of 95.54%. A total of 49 different variants were detected in those patients and we classified 30 rare variants as pathogenic/likely pathogenic, of which 13 were not included in the Clinvar database. Conclusion Our diagnostic panel has an increased diagnostic yield with less cost, and the curated list of pathogenic variants in the SLC26A4 gene can be directly used to aid the genetic counseling to patients. |
| first_indexed | 2024-12-17T23:58:15Z |
| format | Article |
| id | doaj.art-ce3d6348dd6d438c8ace52ddb296038a |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-12-17T23:58:15Z |
| publishDate | 2021-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-ce3d6348dd6d438c8ace52ddb296038a2022-12-21T21:28:01ZengWileyMolecular Genetics & Genomic Medicine2324-92692021-08-0198n/an/a10.1002/mgg3.1734Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next‐generation sequencing of the SLC26A4 geneYongan Tian0Hongen Xu1Danhua Liu2Juanli Zhang3Zengguang Yang4Sen Zhang5Huanfei Liu6Ruijun Li7Yingtao Tian8Beiping Zeng9Tong Li10Qianyu Lin11Haili Wang12Xiaohua Li13Wei Lu14Ying Shi15Yan Zhang16Hui Zhang17Chang Jiang18Ying Xu19Bei Chen20Jun Liu21Wenxue Tang22BGI College Zhengzhou University Zhengzhou ChinaThe Second Affiliated Hospital of Zhengzhou University Zhengzhou ChinaThe Second Affiliated Hospital of Zhengzhou University Zhengzhou ChinaHenan Province Medical Instrument Testing Institute Zhengzhou ChinaSanglin Biotechnology Ltd. Zhengzhou ChinaSchool of Basic Medical Sciences Zhengzhou University Zhengzhou ChinaPrecision Medicine Center Academy of Medical Science Zhengzhou University Zhengzhou ChinaPrecision Medicine Center Academy of Medical Science Zhengzhou University Zhengzhou ChinaSanglin Biotechnology Ltd. Zhengzhou ChinaBGI College Zhengzhou University Zhengzhou ChinaBGI College Zhengzhou University Zhengzhou ChinaSchool of Basic Medical Sciences Zhengzhou University Zhengzhou ChinaNational Health Commission Key Laboratory of Birth Defects Prevention Henan Key Laboratory of Population Defects Prevention Zhengzhou ChinaDepartment of Otology the First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Otology the First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaThe Third Affiliated Hospital of Zhengzhou University Zhengzhou ChinaThe Second Affiliated Hospital of Zhengzhou University Zhengzhou ChinaThe Second Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Otology Henan Provincial People's Hospital Zhengzhou ChinaZhengzhou Children's Hospital Zhengzhou ChinaDepartment of Otology the First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Otology Henan Provincial People's Hospital Zhengzhou ChinaThe Second Affiliated Hospital of Zhengzhou University Zhengzhou ChinaAbstract Background The enlarged vestibular aqueduct (EVA) is the commonest malformation of inner ear accompanied by sensorineural hearing loss in children. Three genes SLC26A4, FOXI1, and KCNJ10 have been associated with EVA, among them SLC26A4 being the most common. Yet, hotspot mutation screening can only diagnose a small number of patients. Methods Thus, in this study, we designed a new molecular diagnosis panel for EVA based on multiplex PCR enrichment and next‐generation sequencing of the exon and flanking regions of SLC26A4. A total of 112 hearing loss families with EVA were enrolled and the pathogenicity of the rare variants detected was interpreted according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Results Our results showed that 107/112 (95.54%) families carried SLC26A4 biallelic mutations, 4/112 (3.57%) carried monoallelic variants, and 1/112 (0.89%) had none variant, resulting in a diagnostic rate of 95.54%. A total of 49 different variants were detected in those patients and we classified 30 rare variants as pathogenic/likely pathogenic, of which 13 were not included in the Clinvar database. Conclusion Our diagnostic panel has an increased diagnostic yield with less cost, and the curated list of pathogenic variants in the SLC26A4 gene can be directly used to aid the genetic counseling to patients.https://doi.org/10.1002/mgg3.1734enlarged vestibular aqueductmultiplex PCRpathogenic variantsSLC26A4 |
| spellingShingle | Yongan Tian Hongen Xu Danhua Liu Juanli Zhang Zengguang Yang Sen Zhang Huanfei Liu Ruijun Li Yingtao Tian Beiping Zeng Tong Li Qianyu Lin Haili Wang Xiaohua Li Wei Lu Ying Shi Yan Zhang Hui Zhang Chang Jiang Ying Xu Bei Chen Jun Liu Wenxue Tang Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next‐generation sequencing of the SLC26A4 gene Molecular Genetics & Genomic Medicine enlarged vestibular aqueduct multiplex PCR pathogenic variants SLC26A4 |
| title | Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next‐generation sequencing of the SLC26A4 gene |
| title_full | Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next‐generation sequencing of the SLC26A4 gene |
| title_fullStr | Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next‐generation sequencing of the SLC26A4 gene |
| title_full_unstemmed | Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next‐generation sequencing of the SLC26A4 gene |
| title_short | Increased diagnosis of enlarged vestibular aqueduct by multiplex PCR enrichment and next‐generation sequencing of the SLC26A4 gene |
| title_sort | increased diagnosis of enlarged vestibular aqueduct by multiplex pcr enrichment and next generation sequencing of the slc26a4 gene |
| topic | enlarged vestibular aqueduct multiplex PCR pathogenic variants SLC26A4 |
| url | https://doi.org/10.1002/mgg3.1734 |
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