{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T10:04:24Z","timestamp":1784801064249,"version":"3.55.0"},"reference-count":68,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,26]],"date-time":"2022-12-26T00:00:00Z","timestamp":1672012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ongoing National Health Program, Ministry of Health, Romania\u2014Prevention of congenital malformations through pre- and post-natal diagnostic","award":["PN.VI.3.3."],"award-info":[{"award-number":["PN.VI.3.3."]}]},{"name":"ongoing National Health Program, Ministry of Health, Romania\u2014Prevention of congenital malformations through pre- and post-natal diagnostic","award":["POCU\/993\/6\/13\/153178"],"award-info":[{"award-number":["POCU\/993\/6\/13\/153178"]}]},{"name":"European Social Fund within the Sectorial Operational Program Human Capital 2014\u20132020","award":["PN.VI.3.3."],"award-info":[{"award-number":["PN.VI.3.3."]}]},{"name":"European Social Fund within the Sectorial Operational Program Human Capital 2014\u20132020","award":["POCU\/993\/6\/13\/153178"],"award-info":[{"award-number":["POCU\/993\/6\/13\/153178"]}]},{"name":"the University of Medicine and Pharmacy of Craiova, Romania","award":["PN.VI.3.3."],"award-info":[{"award-number":["PN.VI.3.3."]}]},{"name":"the University of Medicine and Pharmacy of Craiova, Romania","award":["POCU\/993\/6\/13\/153178"],"award-info":[{"award-number":["POCU\/993\/6\/13\/153178"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The genetic causes of autosomal recessive nonsyndromic hearing loss (ARNSHL) are heterogeneous and highly ethnic-specific. We describe GJB2 (connexin 26) variants and carrier frequencies as part of our study and summarize previously reported ones for the Romanian population. In total, 284 unrelated children with bilateral congenital NSHL were enrolled between 2009 and 2018 in northwestern Romania. A tiered diagnostic approach was used: all subjects were tested for c.35delG, c.71G&gt;A and deletions in GJB6 (connexin 30) using PCR-based methods. Furthermore, 124 cases undiagnosed at this stage were analyzed by multiplex-ligation-dependent probe amplifications (MLPA), probe mix P163, and sequencing of GJB2 exon 2. Targeted allele-specific PCR\/restriction fragment length polymorphism (RFLP) established definite ethio-pathogenical diagnosis for 72\/284 (25.35%) of the cohort. Out of the 124 further analyzed, in 12 cases (9.67%), we found compound heterozygous point mutations in GJB2. We identified one case of deletion of exon 1 of the WFS1 (wolframin) gene. Carrier status evaluation used Illumina Infinium Global Screening Array (GSA) genotyping: the HINT cohort-416 individuals in northwest Romania, and the FUSE cohort-472 individuals in southwest Romania. GSA variants yielded a cumulated risk allele presence of 0.0284. A tiered diagnostic approach may be efficient in diagnosing ARNSHL. The summarized contributions to Romanian descriptive epidemiology of ARNSHL shows that pathogenic variants in the GJB2 gene are frequent among NSHL cases and have high carrier rates, especially for c.35delG and c.71G&gt;A. These findings may serve in health strategy development.<\/jats:p>","DOI":"10.3390\/genes14010069","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T07:30:06Z","timestamp":1672126206000},"page":"69","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Non-Syndromic Hearing Loss in a Romanian Population: Carrier Status and Frequent Variants in the GJB2 Gene"],"prefix":"10.3390","volume":"14","author":[{"given":"Anca-Lelia","family":"Riza","sequence":"first","affiliation":[{"name":"Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania"},{"name":"Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4364-7181","authenticated-orcid":false,"given":"Camelia","family":"Alkhzouz","sequence":"additional","affiliation":[{"name":"First Pediatric Department, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"Clinical Emergency Hospital for Children, 400394 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Farca\u0219","sequence":"additional","affiliation":[{"name":"Molecular Sciences Department, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"P\u00eervu","sequence":"additional","affiliation":[{"name":"Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania"},{"name":"Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Miclea","sequence":"additional","affiliation":[{"name":"First Pediatric Department, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"Clinical Emergency Hospital for Children, 400394 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gheorghe","family":"Mihu\u021b","sequence":"additional","affiliation":[{"name":"ENT Department, Clinical Emergency Hospital for Children, 400394 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2686-3878","authenticated-orcid":false,"given":"R\u0103zvan-Mihail","family":"Ple\u0219ea","sequence":"additional","affiliation":[{"name":"Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania"},{"name":"Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia","family":"\u0218tefan","sequence":"additional","affiliation":[{"name":"Molecular Sciences Department, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Drodar","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u0103lin","family":"Laz\u0103r","sequence":"additional","affiliation":[{"name":"First Pediatric Department, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"Clinical Emergency Hospital for Children, 400394 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"on behalf of the HINT Study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"on behalf of the FUSE Study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai","family":"Ioana","sequence":"additional","affiliation":[{"name":"Regional Centre of Medical Genetics Dolj, Emergency County Hospital Craiova, 200642 Craiova, Romania"},{"name":"Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radu","family":"Popp","sequence":"additional","affiliation":[{"name":"Molecular Sciences Department, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,26]]},"reference":[{"key":"ref_1","unstructured":"WHO (2018). Who Estimates, WHO."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li, H., and Chai, R. (2019). Diagnosis, intervention, and prevention of genetic hearing loss. Hearing Loss: Mechanisms, Prevention and Cure, Springer Singapore.","DOI":"10.1007\/978-981-13-6123-4"},{"key":"ref_3","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."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"a033258","DOI":"10.1101\/cshperspect.a033258","article-title":"The epidemiology of deafness","volume":"9","author":"Sheffield","year":"2019","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s41431-019-0553-8","article-title":"Exome sequencing in infants with congenital hearing impairment: A population-based cohort study","volume":"28","author":"Downie","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1515\/JBCPP.2005.16.2-3.101","article-title":"Connexins in hearing loss: A comprehensive overview","volume":"16","author":"Sabag","year":"2005","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E34","DOI":"10.1002\/lary.24332","article-title":"Gjb2-associated hearing loss: Systematic review of worldwide prevalence, genotype, and auditory phenotype","volume":"124","author":"Chan","year":"2014","journal-title":"Laryngoscope"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/ahg.12354","article-title":"Gjb2-related hearing loss in central iran: Review of the spectrum and frequency of gene mutations","volume":"84","author":"Koohiyan","year":"2020","journal-title":"Ann. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11976","DOI":"10.1038\/s41598-019-47141-4","article-title":"Comprehensive analysis of syndromic hearing loss patients in japan","volume":"9","author":"Ideura","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e182","DOI":"10.1097\/MAO.0000000000002505","article-title":"Systematic review of pathogenic gjb2 variants in the latino population","volume":"41","author":"Bouzaher","year":"2020","journal-title":"Otol. Neurotol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1056\/NEJM199811193392103","article-title":"Mutations in the connexin 26 gene (gjb2) among ashkenazi jews with nonsyndromic recessive deafness","volume":"339","author":"Morell","year":"1998","journal-title":"New Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"383","DOI":"10.11604\/pamj.2015.20.383.5230","article-title":"Genetics of hearing loss in africans: Use of next generation sequencing is the best way forward","volume":"20","author":"Lebeko","year":"2015","journal-title":"Pan Afr. Med. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e488","DOI":"10.1097\/MAO.0000000000002234","article-title":"Systematic review of hearing loss genes in the african american population","volume":"40","author":"Worden","year":"2019","journal-title":"Otol. Neurotol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Aboagye, E.T., Adadey, S.M., Esoh, K., Jonas, M., de Kock, C., Amenga-Etego, L., Awandare, G.A., and Wonkam, A. (2022). Age estimate of gjb2-p.(arg143trp) founder variant in hearing impairment in ghana, suggests multiple independent origins across populations. Biology, 11.","DOI":"10.3390\/biology11030476"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s00441-014-2029-z","article-title":"Connexins and gap junctions in the inner ear--it\u2019s not just about k\u207a recycling","volume":"360","author":"Jagger","year":"2015","journal-title":"Cell Tissue Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"a033233","DOI":"10.1101\/cshperspect.a033233","article-title":"Inner ear connexin channels: Roles in development and maintenance of cochlear function","volume":"9","author":"Mammano","year":"2019","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","unstructured":"Qiu, Y., Zheng, J., Chen, S., and Sun, Y. (2022). Connexin mutations and hereditary diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084255"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"428","DOI":"10.3389\/fnmol.2017.00428","article-title":"Dfnb1 non-syndromic hearing impairment: Diversity of mutations and associated phenotypes","volume":"10","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1080\/14992020802607449","article-title":"Statistical study of 35delg mutation of gjb2 gene: A meta-analysis of carrier frequency","volume":"48","author":"Mahdieh","year":"2009","journal-title":"Int. J. Audiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1159\/000502201","article-title":"Genetics of hereditary hearing loss in the middle east: A systematic review of the carrier frequency of the gjb2 mutation (35delg)","volume":"24","author":"Koohiyan","year":"2019","journal-title":"Audiol. Neurotol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1089\/gte.2005.9.20","article-title":"The 35delg mutation in the connexin 26 gene (gjb2) associated with congenital deafness: European carrier frequencies and evidence for its origin in ancient greece","volume":"9","author":"Lucotte","year":"2005","journal-title":"Genet. Test."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Shinagawa, J., Moteki, H., Nishio, S.Y., Noguchi, Y., and Usami, S.I. (2020). Haplotype analysis of gjb2 mutations: Founder effect or mutational hot spot?. Genes, 11.","DOI":"10.3390\/genes11030250"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"61s","DOI":"10.1177\/0003489415575060","article-title":"Ethnic-specific spectrum of gjb2 and slc26a4 mutations: Their origin and a literature review","volume":"124","author":"Tsukada","year":"2015","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/ahg.12284","article-title":"Update of spectrum c. 35delg and c.-23+ 1g> a mutations on the gjb2 gene in individuals with autosomal recessive nonsyndromic hearing loss","volume":"83","author":"Ahmadi","year":"2019","journal-title":"Ann. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1086\/497996","article-title":"GJB2 mutations and degree of hearing loss: A multicenter study","volume":"77","author":"Snoeckx","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1136\/jmg.2003.013896","article-title":"A genotype-phenotype correlation for gjb2 (connexin 26) deafness","volume":"41","author":"Cryns","year":"2004","journal-title":"J. Med. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1001\/archoto.2009.202","article-title":"Audiologic phenotype and progression in gjb2 (connexin 26) hearing loss","volume":"136","author":"Kenna","year":"2010","journal-title":"Arch. Otolaryngol. \u2013Head Neck Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1046\/j.1529-8817.2003.00120.x","article-title":"Double heterozygosity with mutations involving both the gjb2 and gjb6 genes is a possible, but very rare, cause of congenital deafness in the czech population","volume":"69","author":"Seeman","year":"2005","journal-title":"Ann. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1080\/00016489.2016.1276303","article-title":"Outcomes of cochlear implantation for the patients with specific genetic etiologies: A systematic literature review","volume":"137","author":"Nishio","year":"2017","journal-title":"Acta Oto-Laryngol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1177\/0194599817697054","article-title":"Predictive value of gjb2 mutation status for hearing outcomes of pediatric cochlear implantation","volume":"157","author":"Abdurehim","year":"2017","journal-title":"Otolaryngol. \u2013Head Neck Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ijporl.2009.12.015","article-title":"Prevalence of the c.35delg and p.W24x mutations in the gjb2 gene in patients with nonsyndromic hearing loss from north-west romania","volume":"74","author":"Popp","year":"2010","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wroblewska-Seniuk, K., Greczka, G., Dabrowski, P., Szyfter-Harris, J., and Mazela, J. (2017). Hearing impairment in premature newborns\u2014Analysis based on the national hearing screening database in poland. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0184359"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ijporl.2016.12.029","article-title":"Prevalence and independent risk factors for hearing impairment among very low birth weight infants","volume":"93","author":"Wang","year":"2017","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_35","first-page":"9","article-title":"A polymerase chain reaction-restriction fragment length polymorphism (pcr-rflp) test to detect the common mutation (35delg) in the connexin-26 gene","volume":"3","author":"Simsek","year":"2001","journal-title":"SQU J. Sci. Res. -Med. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/(SICI)1098-1004(1998)11:5<387::AID-HUMU6>3.0.CO;2-8","article-title":"Identification of mutations in the connexin 26 gene that cause autosomal recessive nonsyndromic hearing loss","volume":"11","author":"Scott","year":"1998","journal-title":"Hum. Mutat."},{"key":"ref_37","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_38","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"Varsome: The human genomic variant search engine","volume":"35","author":"Kopanos","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.ajhg.2018.08.006","article-title":"Genomic landscape and mutational signatures of deafness-associated genes","volume":"103","author":"Azaiez","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1002\/humu.24298","article-title":"Annotating and prioritizing genomic variants using the ensembl variant effect predictor\u2014A tutorial","volume":"43","author":"Hunt","year":"2021","journal-title":"Hum. Mutat."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Resmerita, I., Cozma, R.S., Popescu, R., Radulescu, L.M., Panzaru, M.C., Butnariu, L.I., Caba, L., and Ilie, O.D. (2020). Genetics of hearing impairment in north-eastern romania-a cost-effective improved diagnosis and literature review. Genes, 11.","DOI":"10.3390\/genes11121506"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"121","DOI":"10.14740\/ijcp194w","article-title":"Gjb2 gene testing, etiologic diagnosis and genetic counseling in romanian persons with prelingual hearing loss","volume":"4","author":"Dragomir","year":"2015","journal-title":"Int. J. Clin. Pediatr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ijporl.2011.10.007","article-title":"Prevalence of mutations located at the dfnb1 locus in a population of cochlear implanted children in eastern romania","volume":"76","author":"Cozma","year":"2012","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"612","DOI":"10.3892\/etm.2021.10044","article-title":"Prevalence of gjb2 gene mutations correlated to presence of clinical and environmental risk factors in the etiology of congenital sensorineural hearing loss of the romanian population","volume":"21","author":"Neagu","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Safka Brozkova, D., Uhrova Meszarosova, A., Lassuthova, P., Varga, L., Stan\u011bk, D., Boreck\u00e1, S., La\u0161t\u016fvkov\u00e1, J., \u010cejnov\u00e1, V., Ra\u0161kov\u00e1, D., and Lhota, F. (2021). The cause of hereditary hearing loss in gjb2 heterozygotes\u2014A comprehensive study of the gjb2\/dfnb1 region. Genes, 12.","DOI":"10.3390\/genes12050684"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/j.jmoldx.2021.07.007","article-title":"Hearing impairment with monoallelic gjb2 variants: A gjb2 cause or non-gjb2 cause?","volume":"23","author":"Lin","year":"2021","journal-title":"J. Mol. Diagn."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1007\/s00405-018-5083-4","article-title":"Analysis of gjb2 mutations and the clinical manifestation in a large hungarian cohort","volume":"275","author":"Milley","year":"2018","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_49","first-page":"549","article-title":"High frequency of gjb2 mutation w24x among slovak romany (gypsy) patients with non-syndromic hearing loss (nshl)","volume":"22","author":"Ficek","year":"2003","journal-title":"Gen. Physiol. Biophys."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/gte.2007.0048","article-title":"Carrier rates of the ancestral indian w24x mutation in gjb2 in the general gypsy population and individual subisolates","volume":"11","author":"Bouwer","year":"2007","journal-title":"Genet. Test."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1089\/gtmb.2011.0048","article-title":"Prenatal screening for the 35delg gjb2, del (gjb6-d13s1830), and del (gjb6-d13s1854) mutations in the romanian population","volume":"15","author":"Dragomir","year":"2011","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0031-3955(03)00026-9","article-title":"Genetic screening for deafness","volume":"50","author":"Smith","year":"2003","journal-title":"Pediatr. Clin. North Am."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1097\/GIM.0b013e318226fc2e","article-title":"Evaluation of newborn screening bloodspot-based genetic testing as second tier screen for bedside newborn hearing screening","volume":"13","author":"Schimmenti","year":"2011","journal-title":"Genet. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/gim.2016.66","article-title":"Newborn genetic screening for hearing impairment: A population-based longitudinal study","volume":"19","author":"Wu","year":"2017","journal-title":"Genet. Med."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Hao, Z., Fu, D., Ming, Y., Yang, J., Huang, Q., Lin, W., Zhang, H., Zhang, B., Zhou, A., and Hu, X. (2018). Large scale newborn deafness genetic screening of 142,417 neonates in wuhan, china. PLoS One, 13.","DOI":"10.1371\/journal.pone.0195740"},{"key":"ref_56","first-page":"3538","article-title":"Detection of hereditary hearing loss gene by DNA microarray","volume":"21","author":"Han","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"841","DOI":"10.3389\/fgene.2019.00841","article-title":"Gjb2 and gjb6 mutations in non-syndromic childhood hearing impairment in ghana","volume":"10","author":"Adadey","year":"2019","journal-title":"Front. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/jhg.2015.143","article-title":"An effective screening strategy for deafness in combination with a next-generation sequencing platform: A consecutive analysis","volume":"61","author":"Sakuma","year":"2016","journal-title":"J. Hum. Genet."},{"key":"ref_59","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_60","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1038\/s41436-018-0004-x","article-title":"Utility and limitations of exome sequencing as a genetic diagnostic tool for children with hearing loss","volume":"20","author":"Sheppard","year":"2018","journal-title":"Genet. Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Liu, W.-H., Chang, P.-Y., Chang, S.-C., Lu, J.-J., and Wu, C.-M. (2019). Mutation screening in non-syndromic hearing loss patients with cochlear implantation by massive parallel sequencing in taiwan. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0211261"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s12967-019-2018-9","article-title":"Overinterpretation of high throughput sequencing data in medical genetics: First evidence against tmprss3\/gjb2 digenic inheritance of hearing loss","volume":"17","author":"Lechowicz","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1111\/cge.13515","article-title":"Exome sequencing reveals novel variants and unique allelic spectrum for hearing impairment in filipino cochlear implantees","volume":"95","author":"Truong","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"109756","DOI":"10.1016\/j.ijporl.2019.109756","article-title":"Next generation sequencing and genetics of hereditary hearing loss in the iranian population: New insights from a systematic review","volume":"129","author":"Koohiyan","year":"2020","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/s41436-019-0745-1","article-title":"Exome sequencing in newborns with congenital deafness as a model for genomic newborn screening: The baby beyond hearing project","volume":"22","author":"Downie","year":"2020","journal-title":"Genet. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1080\/14737159.2021.1887731","article-title":"Utility of droplet digital pcr and ngs-based cnv clinical assays in hearing loss diagnostics: Current status and future prospects","volume":"21","author":"Rentas","year":"2021","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1080\/14737159.2017.1340834","article-title":"Molecular diagnostics for hereditary hearing loss in children","volume":"17","author":"Sommen","year":"2017","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1007\/s12098-015-1941-x","article-title":"Advances in the understanding of the genetic causes of hearing loss in children inform a rational approach to evaluation","volume":"83","author":"Carey","year":"2016","journal-title":"Indian J. Pediatr."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/1\/69\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:51:18Z","timestamp":1760147478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/1\/69"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,26]]},"references-count":68,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["genes14010069"],"URL":"https:\/\/doi.org\/10.3390\/genes14010069","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,26]]}}}