A novel intronic variant causing aberrant splicing identified in two deaf Chinese siblings with enlarged vestibular aqueducts
Abstract Objective We aimed to evaluate the genotype–phenotype relationship in two Chinese family members with enlarged vestibular aqueduct (EVA). Methods We collected blood samples and clinical data from each pedigree family member. Genomic DNA was isolated from peripheral leukocytes using standard...
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.2361 |
| _version_ | 1827340990070915072 |
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| author | Suyang Wang Yi‐Ming Zhu ChenYang Xu Wenjuan Ding Hui Jia Panpan Bian Baicheng Xu Yufen Guo Xiaowen Liu |
| author_facet | Suyang Wang Yi‐Ming Zhu ChenYang Xu Wenjuan Ding Hui Jia Panpan Bian Baicheng Xu Yufen Guo Xiaowen Liu |
| author_sort | Suyang Wang |
| collection | DOAJ |
| description | Abstract Objective We aimed to evaluate the genotype–phenotype relationship in two Chinese family members with enlarged vestibular aqueduct (EVA). Methods We collected blood samples and clinical data from each pedigree family member. Genomic DNA was isolated from peripheral leukocytes using standard methods. Targeted next‐generation sequencing and Sanger sequencing were performed to find the pathogenic mutation in this family. Minigene assays were used to verify whether the novel intronic mutation SLC26A4c.765+4A>G influenced mRNA splicing. Results Hearing loss in the patients with EVA was diagnosed using auditory tests and imaging examinations. Two pathogenic mutations, c.765+4A>G and c.919‐2A>G were detected in SLC26A4. In vitro minigene analysis confirmed that c.765+4A>G variant could cause aberrant splicing, resulting in skipping over exon 6. Conclusions The SLC26A4c.765+4A>G mutation is the causative variant in the Chinese family with EVA. Particular attention should be paid to intronic variants. |
| first_indexed | 2024-03-07T21:32:26Z |
| format | Article |
| id | doaj.art-1cd562f148bc43639d023abb66e6a0ac |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T21:32:26Z |
| publishDate | 2024-02-01 |
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| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-1cd562f148bc43639d023abb66e6a0ac2024-02-26T14:52:29ZengWileyMolecular Genetics & Genomic Medicine2324-92692024-02-01122n/an/a10.1002/mgg3.2361A novel intronic variant causing aberrant splicing identified in two deaf Chinese siblings with enlarged vestibular aqueductsSuyang Wang0Yi‐Ming Zhu1ChenYang Xu2Wenjuan Ding3Hui Jia4Panpan Bian5Baicheng Xu6Yufen Guo7Xiaowen Liu8Department of Otolaryngology‐Head and Neck Surgery Lanzhou University Second Hospital Lanzhou Gansu PR ChinaDepartment of Otolaryngology‐Head and Neck Surgery Gansu Provincial Hospital Lanzhou Gansu PR ChinaDepartment of Otolaryngology‐Head and Neck Surgery Lanzhou University Second Hospital Lanzhou Gansu PR ChinaDepartment of Otolaryngology‐Head and Neck Surgery Lanzhou University Second Hospital Lanzhou Gansu PR ChinaDepartment of Otolaryngology‐Head and Neck Surgery Lanzhou University Second Hospital Lanzhou Gansu PR ChinaDepartment of Otolaryngology‐Head and Neck Surgery Lanzhou University Second Hospital Lanzhou Gansu PR ChinaDepartment of Otolaryngology‐Head and Neck Surgery Lanzhou University Second Hospital Lanzhou Gansu PR ChinaDepartment of Otolaryngology‐Head and Neck Surgery Lanzhou University Second Hospital Lanzhou Gansu PR ChinaDepartment of Otolaryngology‐Head and Neck Surgery Lanzhou University Second Hospital Lanzhou Gansu PR ChinaAbstract Objective We aimed to evaluate the genotype–phenotype relationship in two Chinese family members with enlarged vestibular aqueduct (EVA). Methods We collected blood samples and clinical data from each pedigree family member. Genomic DNA was isolated from peripheral leukocytes using standard methods. Targeted next‐generation sequencing and Sanger sequencing were performed to find the pathogenic mutation in this family. Minigene assays were used to verify whether the novel intronic mutation SLC26A4c.765+4A>G influenced mRNA splicing. Results Hearing loss in the patients with EVA was diagnosed using auditory tests and imaging examinations. Two pathogenic mutations, c.765+4A>G and c.919‐2A>G were detected in SLC26A4. In vitro minigene analysis confirmed that c.765+4A>G variant could cause aberrant splicing, resulting in skipping over exon 6. Conclusions The SLC26A4c.765+4A>G mutation is the causative variant in the Chinese family with EVA. Particular attention should be paid to intronic variants.https://doi.org/10.1002/mgg3.2361c.765+4A>GEVASLC26A4splicing minigene assay |
| spellingShingle | Suyang Wang Yi‐Ming Zhu ChenYang Xu Wenjuan Ding Hui Jia Panpan Bian Baicheng Xu Yufen Guo Xiaowen Liu A novel intronic variant causing aberrant splicing identified in two deaf Chinese siblings with enlarged vestibular aqueducts Molecular Genetics & Genomic Medicine c.765+4A>G EVA SLC26A4 splicing minigene assay |
| title | A novel intronic variant causing aberrant splicing identified in two deaf Chinese siblings with enlarged vestibular aqueducts |
| title_full | A novel intronic variant causing aberrant splicing identified in two deaf Chinese siblings with enlarged vestibular aqueducts |
| title_fullStr | A novel intronic variant causing aberrant splicing identified in two deaf Chinese siblings with enlarged vestibular aqueducts |
| title_full_unstemmed | A novel intronic variant causing aberrant splicing identified in two deaf Chinese siblings with enlarged vestibular aqueducts |
| title_short | A novel intronic variant causing aberrant splicing identified in two deaf Chinese siblings with enlarged vestibular aqueducts |
| title_sort | novel intronic variant causing aberrant splicing identified in two deaf chinese siblings with enlarged vestibular aqueducts |
| topic | c.765+4A>G EVA SLC26A4 splicing minigene assay |
| url | https://doi.org/10.1002/mgg3.2361 |
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