title: A New Genetic Diagnostic for Enlarged Vestibular Aqueduct Based on Next-Generation Sequencing.
abstract: Enlarged vestibular aqueduct (EVA) is one of the most common congenital inner ear malformations and accounts for 1-12% of sensorineural deafness in children and adolescents. Multiple genetic defects contribute to EVA; therefore, early molecular diagnosis is critical for EVA patients to ensure that the most effective treatment strategies are employed. This study explored a new genetic diagnosis method for EVA and applied it to clinic diagnoses of EVA patients. Using next-generation sequencing technology, we set up a multiple polymerase chain reaction enrichment system for target regions of EVA pathogenic genes (SLC26A4, FOXI1, and KCNJ10). Forty-six EVA samples were sequenced by this system. Variants were detected in 87.0% (40/46) of cases, including three novel variants (SLC26A4 c.923_929del, c.1002-8C>G, and FOXI1 c.519C>A). Biallelic potential pathogenic variants were detected in 27/46 patient samples, leading to a purported diagnostic rate of 59%. All results were verified by Sanger sequencing. Our target region capture system was validated to amplify and measure SLC26A4, FOXI1, and KCNJ10 in one reaction system. The result supplemented the mutation spectrum of EVA. Thus, this strategy is an economic, rapid, accurate, and reliable method with many useful applications in the clinical diagnosis of EVA patients.
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.|The State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Chufeng
authors.initials: C
authors.lastname: He
authors.affiliation: R&D Department, Genesky Diagnostics Inc., Suzhou, Jiangsu, China.
authors.forename: Deyuan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xinzhang
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Mei
mesh_terms: D000293:Adolescent; D000328:Adult; D027321:Anion Transport Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D000076988:Sulfate Transporters; D014723:Vestibular Aqueduct / Q000002:abnormalities*; D000098854:Kcnj10 Channel
chemical_list: D027321:Anion Transport Proteins; C477894:FOXI1 protein, human; D051858:Forkhead Transcription Factors; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; C473560:SLC26A1 protein, human; D000076988:Sulfate Transporters