{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:34:05Z","timestamp":1787236445012,"version":"build-2736575974"},"reference-count":79,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institute of Health Carlos III (ISCIII)","award":["PI19\/00303"],"award-info":[{"award-number":["PI19\/00303"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>A cohort of 128 patients from 118 families diagnosed with non-syndromic or syndromic hearing loss (HL) underwent an exhaustive clinical evaluation. Molecular analysis was performed using targeted next-generation sequencing (NGS) with a custom panel that included 59 genes associated with non-syndromic HL or syndromic HL. Variants were prioritized according to the minimum allele frequency and classified according to the American College of Medical Genetics and Genomics guidelines. Variant(s) responsible for the disease were detected in a 40% of families including autosomal recessive (AR), autosomal dominant (AD) and X-linked patterns of inheritance. We identified pathogenic or likely pathogenic variants in 26 different genes, 15 with AR inheritance pattern, 9 with AD and 2 that are X-linked. Fourteen of the found variants are novel. This study highlights the clinical utility of targeted NGS for sensorineural hearing loss. The optimal panel for HL must be designed according to the spectrum of the most represented genes in a given population and the laboratory capabilities considering the pressure on healthcare.<\/jats:p>","DOI":"10.3390\/genes11121467","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T11:50:49Z","timestamp":1607428249000},"page":"1467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Improving the Management of Patients with Hearing Loss by the Implementation of an NGS Panel in Clinical Practice"],"prefix":"10.3390","volume":"11","author":[{"given":"Gema","family":"Garc\u00eda-Garc\u00eda","sequence":"first","affiliation":[{"name":"Group of Molecular, Cellular and Genomic Biomedicine, IIS-La Fe, 46026 Valencia, Spain"},{"name":"CIBER of Rare Diseases (CIBERER), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Berzal-Serrano","sequence":"additional","affiliation":[{"name":"Group of Molecular, Cellular and Genomic Biomedicine, IIS-La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piedad","family":"Garc\u00eda-D\u00edaz","sequence":"additional","affiliation":[{"name":"ENT Department, Polytechnic and University Hospital La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca","family":"Villanova-Aparisi","sequence":"additional","affiliation":[{"name":"Group of Molecular, Cellular and Genomic Biomedicine, IIS-La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ju\u00e1rez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Group of Molecular, Cellular and Genomic Biomedicine, IIS-La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"de Paula-Vernetta","sequence":"additional","affiliation":[{"name":"ENT Department, Polytechnic and University Hospital La Fe, 46026 Valencia, Spain"},{"name":"Surgery Department, University of Valencia, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Cavall\u00e9-Garrido","sequence":"additional","affiliation":[{"name":"Group of Molecular, Cellular and Genomic Biomedicine, IIS-La Fe, 46026 Valencia, Spain"},{"name":"ENT Department, Polytechnic and University Hospital La Fe, 46026 Valencia, Spain"},{"name":"Surgery Department, University of Valencia, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Jaijo","sequence":"additional","affiliation":[{"name":"Group of Molecular, Cellular and Genomic Biomedicine, IIS-La Fe, 46026 Valencia, Spain"},{"name":"CIBER of Rare Diseases (CIBERER), 28029 Madrid, Spain"},{"name":"Units of Genetics, Polytechnic and University Hospital La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8258-6292","authenticated-orcid":false,"given":"Miguel","family":"Armengot-Carceller","sequence":"additional","affiliation":[{"name":"Group of Molecular, Cellular and Genomic Biomedicine, IIS-La Fe, 46026 Valencia, Spain"},{"name":"ENT Department, Polytechnic and University Hospital La Fe, 46026 Valencia, Spain"},{"name":"Surgery Department, University of Valencia, 46026 Valencia, Spain"},{"name":"CIBER of Respiratory Diseases (CIBERES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7211-9129","authenticated-orcid":false,"given":"Jos\u00e9 M","family":"Mill\u00e1n","sequence":"additional","affiliation":[{"name":"Group of Molecular, Cellular and Genomic Biomedicine, IIS-La Fe, 46026 Valencia, Spain"},{"name":"CIBER of Rare Diseases (CIBERER), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Aller","sequence":"additional","affiliation":[{"name":"Group of Molecular, Cellular and Genomic Biomedicine, IIS-La Fe, 46026 Valencia, Spain"},{"name":"CIBER of Rare Diseases (CIBERER), 28029 Madrid, Spain"},{"name":"Units of Genetics, Polytechnic and University Hospital La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1177\/0194599815591156","article-title":"Massively Parallel Sequencing for Genetic Diagnosis of Hearing Loss: The New Standard of Care","volume":"153","author":"Shearer","year":"2015","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1111\/cge.12339","article-title":"Genotype phenotype correlations for hearing impairment: Approaches to management","volume":"85","author":"Hoefsloot","year":"2014","journal-title":"Clin. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1056\/NEJMra050700","article-title":"Newborn hearing screening\u2014A silent revolution","volume":"354","author":"Morton","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/S0140-6736(05)71047-3","article-title":"Sensorineural hearing loss in children","volume":"365","author":"Smith","year":"2005","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1097\/GIM.0b013e3180980bd0","article-title":"Clinical aspects of hereditary hearing loss","volume":"9","author":"Kochhar","year":"2007","journal-title":"Genet. Med."},{"key":"ref_6","first-page":"347","article-title":"American College of Medical Genetics and Genomics guideline for the clinical evaluation and etiologic diagnosis of hearing loss","volume":"16","author":"Alford","year":"2014","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Delmaghani, S., and El-Amraoui, A. (2020). Inner Ear Gene Therapies Take Off: Current Promises and Future Challenges. J. Clin. Med., 9.","DOI":"10.3390\/jcm9072309"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00439-016-1648-8","article-title":"Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss","volume":"135","author":"Bierer","year":"2016","journal-title":"Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yan, D., Xiang, G., Chai, X., Qing, J., Shang, H., Zou, B., Mittal, R., Shen, J., Smith, R.J.H., and Fan, Y.-S. (2017). Screening of deafness-causing DNA variants that are common in patients of European ancestry using a microarray-based approach. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169219"},{"key":"ref_10","unstructured":"Dom\u00ednguez-Ru\u00edz, M. (2015). Estudio Molecular de Genes Implicados en Hipoacusia No Sindr\u00f3mica Autos\u00f3mica Recesiva Mediante Secuenciaci\u00f3n Sanger y de Nueva Generaci\u00f3n, UAM."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"16783","DOI":"10.1038\/s41598-017-16846-9","article-title":"Combined genetic approaches yield a 48% diagnostic rate in a large cohort of French hearing-impaired patients","volume":"7","author":"Baux","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/humu.22926","article-title":"Whole USH2A Gene Sequencing Identifies Several New Deep Intronic Mutations","volume":"37","author":"Liquori","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/humu.21634","article-title":"Usher syndrome type 2 caused by activation of an USH2A pseudoexon: Implications for diagnosis and therapy","volume":"33","author":"Besnard","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"20","DOI":"10.12688\/wellcomeopenres.10069.1","article-title":"Accurate clinical detection of exon copy number variants in a targeted NGS panel using DECoN","volume":"1","author":"Fowler","year":"2016","journal-title":"Wellcome Open Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1136\/jmg.2004.028324","article-title":"A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment","volume":"42","author":"Alvarez","year":"2005","journal-title":"J. Med. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1093\/hmg\/6.9.1605","article-title":"Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans","volume":"6","author":"Zelante","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1001\/jama.281.23.2211","article-title":"Carrier rates in the midwestern United States for GJB2 mutations causing inherited deafness","volume":"281","author":"Green","year":"1999","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1001\/archotol.127.8.927","article-title":"Connexin 26 gene mutations in congenitally deaf children: Pitfalls for genetic counseling","volume":"127","author":"Marlin","year":"2001","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1016\/S0140-6736(98)11071-1","article-title":"Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: Implications for genetic counselling","volume":"353","author":"Denoyelle","year":"1999","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/387080a0","article-title":"Connexin 26 mutations in hereditary non-syndromic sensorineural deafness","volume":"387","author":"Kelsell","year":"1997","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1056\/NEJM199802193380813","article-title":"Connexin 26 R143W mutation associated with recessive nonsyndromic sensorineural deafness in Africa","volume":"338","author":"Brobby","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1056\/NEJMoa012052","article-title":"A deletion involving the connexin 30 gene in nonsyndromic hearing impairment","volume":"346","author":"Villamar","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1136\/jmg.2006.045765","article-title":"Sensorineural deafness and male infertility: A contiguous gene deletion syndrome","volume":"44","author":"Zhang","year":"2007","journal-title":"J. Med. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/humu.10274","article-title":"Auditory neuropathy in patients carrying mutations in the otoferlin gene (OTOF)","volume":"22","author":"Morera","year":"2003","journal-title":"Hum. Mutat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1136\/jmg.39.7.502","article-title":"Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss","volume":"39","author":"Migliosi","year":"2002","journal-title":"J. Med. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.heares.2012.08.007","article-title":"Prediction of cochlear implant performance by genetic mutation: The spiral ganglion hypothesis","volume":"292","author":"Eppsteiner","year":"2012","journal-title":"Hear. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/ejhg.2009.190","article-title":"Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian families","volume":"18","author":"Shahin","year":"2010","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s00109-001-0310-6","article-title":"Mutations in the TMPRSS3 gene are a rare cause of childhood nonsyndromic deafness in Caucasian patients","volume":"80","author":"Wattenhofer","year":"2002","journal-title":"J. Mol. Med. Berl. Ger."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Miyagawa, M., Nishio, S., Ikeda, T., Fukushima, K., and Usami, S. (2013). Massively parallel DNA sequencing successfully identifies new causative mutations in deafness genes in patients with cochlear implantation and EAS. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075793"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1002\/ajmg.a.31937","article-title":"MYO15A (DFNB3) mutations in Turkish hearing loss families and functional modeling of a novel motor domain mutation","volume":"143","author":"Kalay","year":"2007","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1038\/ejhg.2008.30","article-title":"A mutational analysis of the SLC26A4 gene in Spanish hearing-impaired families provides new insights into the genetic causes of Pendred syndrome and DFNB4 hearing loss","volume":"16","author":"Pera","year":"2008","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/j.1399-0004.2005.00539.x","article-title":"Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK\u2014Implications for genetic testing","volume":"68","author":"Hutchin","year":"2005","journal-title":"Clin. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s00439-004-1227-2","article-title":"Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population","volume":"116","author":"Ouyang","year":"2005","journal-title":"Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kothiyal, P., Cox, S., Ebert, J., Husami, A., Kenna, M.A., Greinwald, J.H., Aronow, B.J., and Rehm, H.L. (2010). High-throughput detection of mutations responsible for childhood hearing loss using resequencing microarrays. BMC Biotechnol., 10.","DOI":"10.1186\/1472-6750-10-10"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1002\/humu.9042","article-title":"Mutations in myosin VIIA (MYO7A) and usherin (USH2A) in Spanish patients with Usher syndrome types I and II, respectively","volume":"20","author":"Beneyto","year":"2002","journal-title":"Hum. Mutat."},{"key":"ref_36","first-page":"367","article-title":"The contribution of GPR98 and DFNB31 genes to a Spanish Usher syndrome type 2 cohort","volume":"19","author":"Besnard","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/humu.22004","article-title":"Non-USH2A mutations in USH2 patients","volume":"33","author":"Besnard","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1086\/341558","article-title":"CDH23 mutation and phenotype heterogeneity: A profile of 107 diverse families with Usher syndrome and nonsyndromic deafness","volume":"71","author":"Astuto","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e55","DOI":"10.1136\/jmg.2006.041764","article-title":"Identification of 14 novel mutations in the long isoform of USH2A in Spanish patients with Usher syndrome type II","volume":"43","author":"Aller","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/mgg3.312","article-title":"Next-generation sequencing reveals the mutational landscape of clinically diagnosed Usher syndrome: Copy number variations, phenocopies, a predominant target for translational read-through, and PEX26 mutated in Heimler syndrome","volume":"5","author":"Neuhaus","year":"2017","journal-title":"Mol. Genet. Genomic Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1002\/ajmg.a.32174","article-title":"A novel nonsense mutation in MYO6 is associated with progressive nonsyndromic hearing loss in a Danish DFNA22 family","volume":"146","author":"Sanggaard","year":"2008","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kwon, T.-J., Oh, S.-K., Park, H.-J., Sato, O., Venselaar, H., Choi, S.Y., Kim, S., Lee, K.-Y., Bok, J., and Lee, S.-H. (2014). The effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non-syndromic hearing loss. Open Biol., 4.","DOI":"10.1098\/rsob.140107"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1136\/jmg.2005.032086","article-title":"Espin gene (ESPN) mutations associated with autosomal dominant hearing loss cause defects in microvillar elongation or organisation","volume":"43","author":"Donaudy","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1038\/ejhg.2016.99","article-title":"An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients","volume":"24","author":"Bonnet","year":"2016","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s10162-006-0033-z","article-title":"A novel TECTA mutation in a Dutch DFNA8\/12 family confirms genotype-phenotype correlation","volume":"7","author":"Plantinga","year":"2006","journal-title":"J. Assoc. Res. Otolaryngol. JARO"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1002\/humu.21512","article-title":"DFNA8\/12 caused by TECTA mutations is the most identified subtype of nonsyndromic autosomal dominant hearing loss","volume":"32","author":"Hildebrand","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E13","DOI":"10.1136\/jmg.38.5.e13","article-title":"A cysteine substitution in the zona pellucida domain of alpha-tectorin results in autosomal dominant, postlingual, progressive, mid frequency hearing loss in a Spanish family","volume":"38","author":"Villamar","year":"2001","journal-title":"J. Med. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1093\/hmg\/3.9.1561","article-title":"A Stickler syndrome gene is linked to chromosome 6 near the COL11A2 gene","volume":"3","author":"Brunner","year":"1994","journal-title":"Hum. Mol. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jcg.2011.01.001","article-title":"Identification of two novel missense WFS1 mutations, H696Y and R703H, in patients with non-syndromic low-frequency sensorineural hearing loss","volume":"38","author":"Sun","year":"2011","journal-title":"J. Genet. Genom. Yi Chuan Xue Bao"},{"key":"ref_50","unstructured":"Escribano, L.B. (2016). Epidemiolog\u00eda Gen\u00e9tica en Pacientes Espa\u00f1oles con Hipoacusia de Herencia Autos\u00f3mica Dominante, Sindr\u00f3mica y No Sindr\u00f3mica, Utilizando Herramientas de Nueva Generaci\u00f3n: Array-CGH y Secuenciaci\u00f3n Masiva, UAM."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1038\/s41598-020-60259-0","article-title":"Prevalence and clinical features of hearing loss caused by EYA4 variants","volume":"10","author":"Shinagawa","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_52","first-page":"76","article-title":"Analyses of loss-of-function mutations of the MITF gene suggest that haploinsufficiency is a cause of Waardenburg syndrome type 2A","volume":"59","author":"Nobukuni","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Wu, C.-C., Tsai, C.-Y., Lin, Y.-H., Chen, P.-Y., Lin, P.-H., Cheng, Y.-F., Wu, C.-M., Lin, Y.-H., Lee, C.-Y., and Erdenechuluun, J. (2019). Genetic Epidemiology and Clinical Features of Hereditary Hearing Impairment in the Taiwanese Population. Genes, 10.","DOI":"10.3390\/genes10100772"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_55","first-page":"2187","article-title":"Whole-exome sequencing identifies novel compound heterozygous mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa","volume":"19","author":"Dopazo","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/j.1399-0004.2005.00481.x","article-title":"Clinical and genetic studies in Spanish patients with Usher syndrome type II: Description of new mutations and evidence for a lack of genotype\u2014Phenotype correlation","volume":"68","author":"Bernal","year":"2005","journal-title":"Clin. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1086\/514899","article-title":"Mutation profile of all 49 exons of the human myosin VIIA gene, and haplotype analysis, in Usher 1B families from diverse origins","volume":"61","author":"Adato","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1007\/s00439-014-1460-2","article-title":"Mutations of 60 known causative genes in 157 families with retinitis pigmentosa based on exome sequencing","volume":"133","author":"Xu","year":"2014","journal-title":"Hum. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1136\/jmg.37.1.41","article-title":"Prevalent connexin 26 gene (GJB2) mutations in Japanese","volume":"37","author":"Abe","year":"2000","journal-title":"J. Med. Genet."},{"key":"ref_60","first-page":"40","article-title":"Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene","volume":"106","author":"Rabionet","year":"2000","journal-title":"Hum. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/j.1399-0004.2007.00833.x","article-title":"Distribution and frequencies of CDH23 mutations in Japanese patients with non-syndromic hearing loss","volume":"72","author":"Wagatsuma","year":"2007","journal-title":"Clin. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1159\/000313282","article-title":"Progressive sensorineural hearing loss and normal vestibular function in a Dutch DFNB7\/11 family with a novel mutation in TMC1","volume":"16","author":"Collin","year":"2011","journal-title":"Audiol. Neurootol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.2741\/4046","article-title":"Autosomal recessive nonsyndromic deafness genes: A review","volume":"17","author":"Duman","year":"2012","journal-title":"Front. Biosci."},{"key":"ref_64","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J., Stephens, K., and Amemiya, A. (1993). Hereditary Hearing Loss and Deafness Overview. GeneReviews, University of Washington."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.jmoldx.2014.06.003","article-title":"Comprehensive diagnostic testing for stereocilin: An approach for analyzing medically important genes with high homology","volume":"16","author":"Mandelker","year":"2014","journal-title":"J. Mol. Diagn."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6240","DOI":"10.1073\/pnas.082515999","article-title":"Otoancorin, an inner ear protein restricted to the interface between the apical surface of sensory epithelia and their overlying acellular gels, is defective in autosomal recessive deafness DFNB22","volume":"99","author":"Zwaenepoel","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3892\/mmr.2016.5226","article-title":"Molecular study of patients with auditory neuropathy","volume":"14","author":"Carvalho","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Yokota, Y., Moteki, H., Nishio, S., Yamaguchi, T., Wakui, K., Kobayashi, Y., Ohyama, K., Miyazaki, H., Matsuoka, R., and Abe, S. (2019). Frequency and clinical features of hearing loss caused by STRC deletions. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-40586-7"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3109\/14992027.2014.944276","article-title":"The role and spectrum of SLC26A4 mutations in Iranian patients with autosomal recessive hereditary deafness","volume":"54","author":"Yazdanpanahi","year":"2015","journal-title":"Int. J. Audiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1167\/iovs.09-4085","article-title":"Microarray-based mutation analysis of 183 Spanish families with Usher syndrome","volume":"51","author":"Jaijo","year":"2010","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1001\/jamaophthalmol.2014.4498","article-title":"Clinical aspects of Usher syndrome and the USH2A gene in a cohort of 433 patients","volume":"133","author":"Jaijo","year":"2015","journal-title":"JAMA Ophthalmol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1093\/jalm\/jfaa021","article-title":"Development and Validation of a Next-Generation Sequencing Panel for Syndromic and Nonsyndromic Hearing Loss","volume":"5","author":"Butz","year":"2020","journal-title":"J. Appl. Lab. Med."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Cabanillas, R., Di\u00f1eiro, M., Cifuentes, G.A., Castillo, D., Pruneda, P.C., \u00c1lvarez, R., S\u00e1nchez-Dur\u00e1n, N., Cap\u00edn, R., Plasencia, A., and Viejo-D\u00edaz, M. (2018). Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients. BMC Med. Genom., 11.","DOI":"10.1186\/s12920-018-0375-5"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Diaz-Horta, O., Duman, D., Foster, J., S\u0131rmac\u0131, A., Gonzalez, M., Mahdieh, N., Fotouhi, N., Bonyadi, M., Cengiz, F.B., and Menendez, I. (2012). Whole-exome sequencing efficiently detects rare mutations in autosomal recessive nonsyndromic hearing loss. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050628"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.heares.2016.01.018","article-title":"A next-generation sequencing gene panel (MiamiOtoGenes) for comprehensive analysis of deafness genes","volume":"333","author":"Tekin","year":"2016","journal-title":"Hear. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1111\/cge.13638","article-title":"Whole-exome sequencing identifies rare pathogenic and candidate variants in sporadic Chinese Han deaf patients","volume":"97","author":"Zou","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.ejmg.2017.07.016","article-title":"Reporting practices for variants of uncertain significance from next generation sequencing technologies","volume":"60","author":"Vears","year":"2017","journal-title":"Eur. J. Med. Genet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1755-8166-6-19","article-title":"Genetic testing for hearing loss in the United States should include deletion\/duplication analysis for the deafness\/infertility locus at 15q15.3","volume":"6","author":"Hoppman","year":"2013","journal-title":"Mol. Cytogenet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.heares.2019.01.003","article-title":"Hereditary hearing loss; about the known and the unknown","volume":"376","author":"Kremer","year":"2019","journal-title":"Hear. Res."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/12\/1467\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:42:04Z","timestamp":1760179324000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/12\/1467"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,7]]},"references-count":79,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["genes11121467"],"URL":"https:\/\/doi.org\/10.3390\/genes11121467","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,7]]}}}