{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:37:54Z","timestamp":1780591074093,"version":"3.54.1"},"reference-count":91,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This study was supported by the Ministry of Science and Higher Education of the Russian Federation","award":["FSRG-2023-0003"],"award-info":[{"award-number":["FSRG-2023-0003"]}]},{"name":"YSC CMP project","award":["\u201cStudy of the genetic structure and burden of hereditary pathology of the populations of the Republic of Sakha (Yakutia)\u201d"],"award-info":[{"award-number":["\u201cStudy of the genetic structure and burden of hereditary pathology of the populations of the Republic of Sakha (Yakutia)\u201d"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The audiological features of hearing loss (HL) in patients with autosomal recessive deafness type 1A (DFNB1A) caused by splice site variants of the <jats:italic>GJB2<\/jats:italic> gene are less studied than those of patients with other variants of this gene. In this study, we present the audiological features of DFNB1A in a large cohort of 134 patients with the homozygous splice site variant c.-23+1G&gt;A and 34 patients with other biallelic <jats:italic>GJB2<\/jats:italic> genotypes (n = 168 patients with DFNB1A). We found that the preservation of hearing thresholds in the speech frequency range (PTA<jats:sub>0.5,1.0,2.0,4.0 kHz<\/jats:sub>) in patients with the c.[-23+1G&gt;A];[-23+1G&gt;A] genotype is significantly better than in patients with the \u201csevere\u201d c.[35delG];[35delG] genotype (<jats:italic>p<\/jats:italic> = 0.005) and significantly worse than in patients with the \u201cmild\u201d c.[109G&gt;A];[109G&gt;A] genotype (<jats:italic>p =<\/jats:italic> 0.041). This finding indicates a \u201cmedium\u201d pathological effect of this splice site variant on hearing function. A detailed clinical and audiological analysis showed that in patients with the c.[-23+1G&gt;A];[-23+1G&gt;A] genotype, HL is characterized as congenital or early onset (57.5% onset before 12 months), sensorineural (97.8%), bilateral, symmetrical (82.8%), variable in severity (from mild to profound HL, median hearing threshold in PTA<jats:sub>0.5,1.0,2.0,4.0 kHz<\/jats:sub> is 86.73\u00b121.98 dB), with an extremely \u201cflat\u201d audioprofile, and with a tendency toward slow progression (a positive correlation of hearing thresholds with age, <jats:italic>r<\/jats:italic> = 0.144, <jats:italic>p<\/jats:italic> = 0.041). In addition, we found that the hearing thresholds in PTA<jats:sub>0.5,1.0,2.0,4.0 kHz<\/jats:sub> were significantly better preserved in females (82.34 dB) than in males (90.62 dB) (<jats:italic>p =<\/jats:italic> 0.001). We can conclude that in patients with DFNB1A caused by the c.-23+1G&gt;A variant, male sex is associated with deteriorating auditory function; in contrast, female sex is a protective factor.<\/jats:p>","DOI":"10.1371\/journal.pone.0309439","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T17:34:23Z","timestamp":1729618463000},"page":"e0309439","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genotype\u2013phenotype analysis of hearing function in patients with DFNB1A caused by the c.-23+1G&gt;A splice site variant of the GJB2 gene (Cx26)"],"prefix":"10.1371","volume":"19","author":[{"given":"Fedor M.","family":"Teryutin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera G.","family":"Pshennikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisen V.","family":"Solovyev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgii P.","family":"Romanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sardana A.","family":"Fedorova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6984-7934","authenticated-orcid":true,"given":"Nikolay A.","family":"Barashkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"pone.0309439.ref001","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1749-6632.1991.tb19572.x","article-title":"Genetic epidemiology of hearing impairment","volume":"630","author":"NE Morton","year":"1991","journal-title":"Acad Sci"},{"key":"pone.0309439.ref002","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/ajmg.1320460504","article-title":"Genetic epidemiological studies of early-onset deafness in the U.S. school-age population","volume":"46","author":"ML Marazita","year":"1993","journal-title":"Am J Med Genet"},{"key":"pone.0309439.ref003","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMra050700","article-title":"Newborn Hearing Screening\u2014a Silent Revolution","volume":"354","author":"CC Morton","year":"2006","journal-title":"The New England journal of medicine"},{"key":"pone.0309439.ref004","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000134183","article-title":"Assignment of connexin 26 (GJB2) and 46 (GJA3) genes to human chromosomes 13q11-q12 and mouse chromosome 14D1-E1 by in situ hybridization","volume":"72","author":"C Mignon","year":"1996","journal-title":"Cytogenet Cell Genet"},{"key":"pone.0309439.ref005","first-page":"1993","volume-title":"GeneReviews\u00ae","author":"RJH Smith","year":"1998"},{"key":"pone.0309439.ref006","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/BF00186783","article-title":"Gap junctions in the rat cochlea: immunohistochemical and ultrastructural analysis","volume":"191","author":"T Kikuchi","year":"1995","journal-title":"Anat Embryol (Berl)"},{"key":"pone.0309439.ref007","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":"DP Kelsell","year":"1997","journal-title":"Nature"},{"key":"pone.0309439.ref008","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":"DK Chan","year":"2014","journal-title":"Laryngoscope"},{"key":"pone.0309439.ref009","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3390\/life10110258","article-title":"Connexin Genes Variants Associated with Non-Syndromic Hearing Impairment: A Systematic Review of the Global Burden","volume":"10","author":"SM Adadey","year":"2020","journal-title":"Life"},{"key":"pone.0309439.ref010","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1007\/s00439-021-02425-6","article-title":"Genetic Etiology of Non-Syndromic Hearing Loss in Europe","volume":"141","author":"I Del Castillo","year":"2022","journal-title":"Hum Genet"},{"key":"pone.0309439.ref011","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nature07869","article-title":"Structure of the connexin 26 gap junction channel at 3.5 A resolution","volume":"458","author":"S Maeda","year":"2009","journal-title":"Nature"},{"key":"pone.0309439.ref012","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/ncb1205","article-title":"Impaired permeability to Ins(1,4,5)P3 in a mutant connexin underlies recessive hereditary deafness","volume":"7","author":"M Beltramello","year":"2005","journal-title":"Nat Cell Biol"},{"key":"pone.0309439.ref013","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ceca.2006.05.005","article-title":"Purinergic signalling and intercellular Ca2+ wave propagation in the organ of Corti","volume":"41","author":"V Piazza","year":"2007","journal-title":"Cell Calcium"},{"key":"pone.0309439.ref014","doi-asserted-by":"crossref","first-page":"15201","DOI":"10.1073\/pnas.0501859102","article-title":"Gap junction-mediated intercellular biochemical coupling in cochlear supporting cells is required for normal cochlear functions","volume":"102","author":"Y Zhang","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0309439.ref015","doi-asserted-by":"crossref","first-page":"18724","DOI":"10.1073\/pnas.0506481102","article-title":"Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear","volume":"102","author":"HB Zhao","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0309439.ref016","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.neuroscience.2008.08.027","article-title":"Postnatal development of the organ of Corti in dominant-negative Gjb2 transgenic mice","volume":"156","author":"A Inoshita","year":"2008","journal-title":"Neuroscience"},{"key":"pone.0309439.ref017","doi-asserted-by":"crossref","first-page":"1208406","DOI":"10.3389\/fncel.2023.1208406","article-title":"Research progress in delineating the pathological mechanisms of GJB2-related hearing loss","volume":"17","author":"Y Wang","year":"2023","journal-title":"Front Cell Neurosci"},{"key":"pone.0309439.ref018","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1136\/jmg.2003.013896","article-title":"Genotype-phenotype correlation for GJB2 (connexin 26) deafness","volume":"41","author":"K Cryns","year":"2004","journal-title":"J Med Genet"},{"key":"pone.0309439.ref019","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":"RL Snoeckx","year":"2005","journal-title":"Am J Hum Genet"},{"key":"pone.0309439.ref020","first-page":"829","article-title":"Cx26 deafness: mutation analysis and clinical variability","volume":"36","author":"A Murgia","year":"1999","journal-title":"J Med Genet"},{"key":"pone.0309439.ref021","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/humu.20084","article-title":"GJB2: the spectrum of deafness-causing allele variants and their phenotype","volume":"24","author":"H Azaiez","year":"2004","journal-title":"Hum Mutat"},{"key":"pone.0309439.ref022","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1001\/archotol.131.6.481","article-title":"GJB2 and GJB6 mutations: genotypic and phenotypic correlations in a large cohort of hearing-impaired patients","volume":"131","author":"S Marlin","year":"2005","journal-title":"Arch Otolaryngol Head Neck Surg"},{"key":"pone.0309439.ref023","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s10038-004-0223-7","article-title":"Clinical features of patients with GJB2 (connexin 26) mutations: severity of HL is correlated with genotypes and protein expression patterns","volume":"50","author":"T Oguchi","year":"2005","journal-title":"J Hum Genet"},{"key":"pone.0309439.ref024","doi-asserted-by":"crossref","first-page":"e59624","DOI":"10.1371\/journal.pone.0059624","article-title":"Etiology and audiological outcomes at 3 years for 364 children in Australia","volume":"8","author":"HHM Dahl","year":"2013","journal-title":"PLoS One"},{"key":"pone.0309439.ref025","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1002\/ajmg.a.31982","article-title":"M34T and V37I mutations in GJB2 associated hearing impairment: evidence for pathogenicity and reduced penetrance","volume":"143A","author":"A Pollak","year":"2007","journal-title":"Am J Med Genet A"},{"key":"pone.0309439.ref026","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1002\/lary.20162","article-title":"Audiologic and temporal bone imaging findings in patients with sensorineural HL and GJB2 mutations","volume":"119","author":"KH Lee","year":"2009","journal-title":"Laryngoscope"},{"key":"pone.0309439.ref027","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1089\/gtmb.2008.0086","article-title":"Analysis of the GJB2 and GJB6 genes in Italian patients with nonsyndromic hearing loss: frequencies, novel mutations, genotypes, and degree of hearing loss","volume":"13","author":"P Primignani","year":"2009","journal-title":"Genet Test Mol Biomarkers"},{"key":"pone.0309439.ref028","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1097\/GIM.0b013e3181d0d42b","article-title":"Connexin-26-associated deafness: phenotypic variability and progression of hearing loss","volume":"12","author":"DK Chan","year":"2010","journal-title":"Genet Med"},{"key":"pone.0309439.ref029","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1159\/000297216","article-title":"GJB2 mutations and genotype-phenotype correlation in 335 patients from germany with nonsyndromic sensorineural hearing loss: evidence for additional recessive mutations not detected by current methods","volume":"15","author":"O Bartsch","year":"2010","journal-title":"Audiol Neurootol"},{"key":"pone.0309439.ref030","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":"MA Kenna","year":"2010","journal-title":"Arch Otolaryngol Head Neck Surg"},{"key":"pone.0309439.ref031","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1111\/j.1399-0004.2010.01407.x","article-title":"A large cohort study of GJB2 mutations in Japanese hearing loss patients","volume":"78","author":"K Tsukada","year":"2010","journal-title":"Clin Genet"},{"key":"pone.0309439.ref032","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1002\/ajmg.a.33698","article-title":"Genotype-phenotype correlation of two prevalent GJB2 mutations in Chinese newborn infants ascertained from the Universal Newborn Hearing Screening Program","volume":"152A","author":"Y Ma","year":"2010","journal-title":"Am J Med Genet A"},{"key":"pone.0309439.ref033","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1089\/gtmb.2010.0192","article-title":"Phenotype-genotype correlation in 295 Chinese deaf subjects with biallelic causative mutations in the GJB2 gene","volume":"15","author":"FF Zhao","year":"2011","journal-title":"Genet Test Mol Biomarkers"},{"key":"pone.0309439.ref034","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1007\/s00405-014-2970-1","article-title":"A genotype-phenotype correlation in Sicilian patients with GJB2 biallelic mutations","volume":"272","author":"F Martines","year":"2015","journal-title":"Eur Arch Otorhinolaryngol"},{"key":"pone.0309439.ref035","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1159\/000368292","article-title":"Vestibular functions of hereditary hearing loss patients with GJB2 mutations","volume":"20","author":"K Tsukada","year":"2015","journal-title":"Audiol Neurootol"},{"key":"pone.0309439.ref036","doi-asserted-by":"crossref","first-page":"e0128691","DOI":"10.1371\/journal.pone.0128691","article-title":"GJB2 Mutation Spectrum and Genotype-Phenotype Correlation in 1067 Han Chinese Subjects with Non-Syndromic HL","volume":"10","author":"J Zheng","year":"2015","journal-title":"Plos One"},{"key":"pone.0309439.ref037","doi-asserted-by":"crossref","first-page":"e0129662","DOI":"10.1371\/journal.pone.0129662","article-title":"The Relationship between the p.V37I Mutation in GJB2 and Hearing Phenotypes in Chinese Individuals","volume":"10","author":"S Huang","year":"2015","journal-title":"PLoS One"},{"key":"pone.0309439.ref038","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.heares.2016.01.006","article-title":"Prevalence and audiological profiles of GJB2 mutations in a large collective of hearing impaired patients","volume":"333","author":"WF Burke","year":"2016","journal-title":"Hear Res"},{"key":"pone.0309439.ref039","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ijporl.2017.09.011","article-title":"GJB2 mutations: Genotypic and phenotypic correlation in a cohort of 690 hearing-impaired patients, toward a new mutation?","volume":"102","author":"JC Lecl\u00e8re","year":"2017","journal-title":"Int J Pediatr Otorhinolaryngol"},{"key":"pone.0309439.ref040","doi-asserted-by":"crossref","first-page":"46681","DOI":"10.18632\/oncotarget.17325","article-title":"Association between the p.V37I variant of GJB2 and HL: a pedigree and meta-analysis","volume":"8","author":"N Shen","year":"2017","journal-title":"Oncotarget"},{"key":"pone.0309439.ref041","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":"CC Wu","year":"2017","journal-title":"Genet Med"},{"key":"pone.0309439.ref042","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/j.anl.2020.05.008","article-title":"Differences in hearing levels between siblings with HL caused by GJB2 mutations","volume":"47","author":"M Fujioka","year":"2020","journal-title":"Auris Nasus Larynx"},{"key":"pone.0309439.ref043","first-page":"8841522","article-title":"Hearing Phenotypes of Patients with Hearing Loss Homozygous for the GJB2 c.235delc Mutation","volume":"1","author":"C Guo","year":"2020","journal-title":"Neural Plast"},{"key":"pone.0309439.ref044","doi-asserted-by":"crossref","first-page":"110840","DOI":"10.1016\/j.ijporl.2021.110840","article-title":"Investigation of the hearing levels of siblings affected by a single GJB2 variant: Possibility of genetic modifiers","volume":"149","author":"M Hosoya","year":"2021","journal-title":"Int. J. Pediatr. Otorhinolaryngol"},{"key":"pone.0309439.ref045","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.3390\/jpm12111843","article-title":"Audiological Evidence of Frequent Hereditary Mild, Moderate and Moderate-to-Severe Hearing Loss","volume":"12","author":"T Markova","year":"2022","journal-title":"J Pers Med"},{"key":"pone.0309439.ref046","doi-asserted-by":"crossref","first-page":"16763","DOI":"10.3390\/ijms242316763","article-title":"Hearing and Hearing Loss Progression in Patients with GJB2 Gene Mutations: A Long-Term Follow-Up","volume":"24","author":"A Sakata","year":"2023","journal-title":"Int. J. Mol. Sci"},{"key":"pone.0309439.ref047","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1089\/109065700750065063","article-title":"The M34T allele variant of connexin 26","volume":"4","author":"RA Cucci","year":"2000","journal-title":"Genet Test"},{"key":"pone.0309439.ref048","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1136\/jmg.38.1.20","article-title":"Genetic analysis of the connexin-26 M34T variant: identification of genotype M34T\/M34T segregating with mild-moderate non-syndromic sensorineural hearing loss","volume":"38","author":"MJ Houseman","year":"2001","journal-title":"J Med Genet"},{"key":"pone.0309439.ref049","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/j.1399-0004.2004.00325.x","article-title":"High prevalence of V37I genetic variant in the connexin-26 (GJB2) gene among non-syndromic hearing-impaired and control Thai individuals","volume":"66","author":"D Wattanasirichaigoon","year":"2004","journal-title":"Clin Genet"},{"key":"pone.0309439.ref050","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1002\/ajmg.a.31486","article-title":"V37I connexin 26 allele in patients with sensorineural HL: evidence of its pathogenicity","volume":"140","author":"C Huculak","year":"2006","journal-title":"Am J Med Genet A"},{"key":"pone.0309439.ref051","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s00439-010-0856-x","article-title":"Prospective variants screening of connexin genes in children with hearing impairment: genotype\/phenotype correlation","volume":"128","author":"JJ Yang","year":"2010","journal-title":"Hum Genet"},{"key":"pone.0309439.ref052","doi-asserted-by":"crossref","first-page":"e61592","DOI":"10.1371\/journal.pone.0061592","article-title":"Prevalence of p.V37I Variant of GJB2 in Mild or Moderate HL in a Pediatric Population and the Interpretation of Its Pathogenicity","volume":"8","author":"SY Kim","year":"2013","journal-title":"PLoS One"},{"key":"pone.0309439.ref053","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/cge.12387","article-title":"The homozygous p.V37I variant of GJB2 is associated with diverse hearing phenotypes","volume":"87","author":"Y Chai","year":"2015","journal-title":"Clin Genet"},{"key":"pone.0309439.ref054","doi-asserted-by":"crossref","first-page":"220","DOI":"10.5582\/bst.2016.01096","article-title":"Analysis of p.V37I compound heterozygous mutations in the GJB2 gene in Chinese infants and young children","volume":"10","author":"Y Du","year":"2016","journal-title":"Biosci Trends"},{"key":"pone.0309439.ref055","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/AUD.0000000000000742","article-title":"Prediction Model for Audiological Outcomes in Patients With GJB2 Mutations","volume":"41","author":"PY Chen","year":"2020","journal-title":"Ear Hear"},{"key":"pone.0309439.ref056","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.gim.2021.12.007","article-title":"Biallelic p.V37I variant in GJB2 is associated with increasing incidence of HL with age","volume":"24","author":"Y Chen","year":"2022","journal-title":"Genet Med"},{"key":"pone.0309439.ref057","doi-asserted-by":"crossref","first-page":"108135","DOI":"10.1016\/j.heares.2020.108135","article-title":"GJB2 mutation spectrum in the Taiwanese population and genotype-phenotype comparisons in patients with HL carrying GJB2 c.109G>A and c.235delC mutations","volume":"413","author":"YF Lin","year":"2022","journal-title":"Hear Res"},{"key":"pone.0309439.ref058","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1097\/AUD.0000000000001384","article-title":"GJB2 p.V37I Mutation Associated With Moderate Nonsyndromic Hearing Loss in an Adult Taiwanese Population","volume":"44","author":"TT Yen","year":"2023","journal-title":"Ear Hear"},{"key":"pone.0309439.ref059","first-page":"14","article-title":"Genotypic and Allelic Frequencies of GJB2 Variants and Features of Hearing Phenotypes in the Chinese Population of the Dongfeng-Tongji Cohort","volume":"27","author":"L Yuan","year":"2023","journal-title":"Genes (Basel)"},{"key":"pone.0309439.ref060","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s00439-022-02479-0","article-title":"Comprehensive interpretation of single-nucleotide substitutions in GJB2 reveals the genetic and phenotypic landscape of GJB2-related hearing loss","volume":"142","author":"J Xiang","year":"2023","journal-title":"Hum Genet"},{"key":"pone.0309439.ref061","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":"F Denoyelle","year":"1999","journal-title":"Lancet"},{"key":"pone.0309439.ref062","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":"GE Green","year":"1999","journal-title":"JAMA"},{"issue":"9","key":"pone.0309439.ref063","doi-asserted-by":"crossref","first-page":"e73566","DOI":"10.1371\/journal.pone.0073566","article-title":"A novel splice-site mutation in the GJB2 gene causing mild postlingual hearing impairment","volume":"8","author":"M Gand\u00eda","year":"2013","journal-title":"PLoS One"},{"key":"pone.0309439.ref064","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/jhg.2011.72","article-title":"Autosomal recessive deafness 1A (DFNB1A) in Yakut population isolate in Eastern Siberia: Extensive accumulation of the splice site mutation IVS1+1G>A in GJB2 gene as a result of founder effect","volume":"56","author":"NA Barashkov","year":"2011","journal-title":"J Hum Genet"},{"key":"pone.0309439.ref065","doi-asserted-by":"crossref","first-page":"e0156300","DOI":"10.1371\/journal.pone.0156300","article-title":"Spectrum and Frequency of the GJB2 Gene Pathogenic Variants in a Large Cohort of Patients with Hearing Impairment Living in a Subarctic Region of Russia (the Sakha Republic)","volume":"25","author":"NA Barashkov","year":"2016","journal-title":"PLoS One"},{"key":"pone.0309439.ref066","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/jhg.2017.42","article-title":"Update of the GJB2\/DFNB1 mutation spectrum in Russia: A founder Ingush mutation del(GJB2-D13S175) is the most frequent among other large deletions","volume":"62","author":"EA Bliznetz","year":"2017","journal-title":"J Hum Genet"},{"key":"pone.0309439.ref067","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1134\/S1022795418050071","article-title":"Marital Structure, Genetic Fitness, and the GJB2 Gene Mutations among Deaf People in Yakutia (Eastern Siberia, Russia)","volume":"54","author":"G.P. Romanov","year":"2018","journal-title":"Russian Journal of Genetics"},{"issue":"7","key":"pone.0309439.ref068","first-page":"493","article-title":"Uses and abuses of HL classification","volume":"23","author":"JG Clark","year":"1981","journal-title":"ASHA"},{"key":"pone.0309439.ref069","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/BF02935334","article-title":"The c.IVS1+1G>A mutation in the GJB2 gene is prevalent and large deletions involving the GJB6 gene are not present in the Turkish population","volume":"85","author":"A Sirmaci","year":"2006","journal-title":"J Genet"},{"key":"pone.0309439.ref070","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1086\/301807","article-title":"Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss","volume":"62","author":"PM Kelley","year":"1998","journal-title":"Am J Hum Genet"},{"key":"pone.0309439.ref071","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":"L Zelante","year":"1997","journal-title":"Hum Mol Genet"},{"key":"pone.0309439.ref072","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":"FJ del Castillo","year":"2005","journal-title":"J Med Genet"},{"key":"pone.0309439.ref073","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s12687-017-0299-3","article-title":"Opinions of hearing parents about the causes of hearing impairment of their children with biallelic GJB2 mutations","volume":"8","author":"AV Solovyev","year":"2017","journal-title":"J Community Genet"},{"key":"pone.0309439.ref074","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1097\/01.aud.0000240492.78561.d3","article-title":"Does universal newborn hearing screening identify all children with GJB2 (Connexin 26) deafness? Penetrance of GJB2 deafness","volume":"27","author":"VW Norris","year":"2006","journal-title":"Ear Hear"},{"key":"pone.0309439.ref075","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.gene.2013.08.094","article-title":"GJB2-associated hearing loss undetected by hearing screening of newborns","volume":"532","author":"SB Minami","year":"2013","journal-title":"Gene"},{"key":"pone.0309439.ref076","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/j.1749-4486.2008.01754.x","article-title":"Spectrum of GJB2 mutations causing deafness in the British Bangladeshi population","volume":"33","author":"Y Bajaj","year":"2008","journal-title":"Clin Otolaryngol"},{"key":"pone.0309439.ref077","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.3390\/genes14051001","article-title":"The GJB2 (Cx26) Gene Variants in Patients with Hearing Impairment in the Baikal Lake Region (Russia)","volume":"14","author":"VG Pshennikova","year":"2023","journal-title":"Genes (Basel)"},{"key":"pone.0309439.ref078","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0006-291X(02)00891-4","article-title":"Hearing loss: frequency and functional studies of the most common connexin26 alleles","volume":"296","author":"P D\u2019Andrea","year":"2002","journal-title":"Biochem Biophys Res Commun"},{"key":"pone.0309439.ref079","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s00439-001-0674-2","article-title":"Genetics of congenital deafness in the Palestinian population: multiple connexin 26 alleles with shared origins in the Middle East","volume":"110","author":"H Shahin","year":"2002","journal-title":"Hum Genet"},{"key":"pone.0309439.ref080","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/ejhg.2008.201","article-title":"Phenotypic variability of patients homozygous for the GJB2 mutation 35delG cannot be explained by the influence of one major modifier gene","volume":"17","author":"N Hilgert","year":"2009","journal-title":"Eur J Hum Genet"},{"key":"pone.0309439.ref081","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","author":"FJ Del Castillo","year":"2017","journal-title":"Front Mol Neurosci"},{"key":"pone.0309439.ref082","first-page":"224","article-title":"Association Between Susceptibility to SSHL and Single Nucleotide Polymorphisms at the rs2228612 Locus of the DNMT1 Gene and the rs5570459 Locus of the GJB2 Gene","volume":"29","author":"Y Zhang","year":"2023","journal-title":"Altern Ther Health Med"},{"key":"pone.0309439.ref083","article-title":"Genetic Factors Contribute to the Phenotypic Variability in GJB2-Related Hearing Impairment","volume":"7","author":"YT Chiang","year":"2023","journal-title":"J Mol Diagn"},{"key":"pone.0309439.ref084","doi-asserted-by":"crossref","unstructured":"Maccoby E, Jacklin C. The psychology of sex differences. 1974; Stanford UP, Stanford, CA. 634P. ISBN 0804708592","DOI":"10.1515\/9781503620780"},{"key":"pone.0309439.ref085","doi-asserted-by":"crossref","first-page":"504","DOI":"10.3758\/BF03200938","article-title":"Sex differences in visuospatial ability: do performance factors play such an important role?","volume":"24","author":"AR Delgado","year":"1996","journal-title":"Mem Cognit"},{"key":"pone.0309439.ref086","doi-asserted-by":"crossref","unstructured":"Caplan PJ, Crawford M, Hyde JS, Richardson JTE. Gender differences in human cognition, 1997. Oxford UP. New York. 192P. ISBN 9780195354546","DOI":"10.1093\/acprof:oso\/9780195112917.001.0001"},{"key":"pone.0309439.ref087","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1037\/0735-7044.111.4.845","article-title":"A large sex difference on a two-dimensional mental rotation task","volume":"111","author":"DW Collins","year":"1997","journal-title":"Behav Neurosci"},{"key":"pone.0309439.ref088","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1006\/brcg.1997.0872","article-title":"Sex differences in visual recognition memory: support for a sex-related difference in attention in adults and children","volume":"34","author":"RF McGivern","year":"1997","journal-title":"Brain Cogn"},{"key":"pone.0309439.ref089","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1126\/science.935879","article-title":"Sex and the single hemisphere: specialization of the right hemisphere for spatial processing","volume":"193","author":"DF Witelson","year":"1976","journal-title":"Science"},{"key":"pone.0309439.ref090","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1080\/01688639508405148","article-title":"Is there a sex difference in human laterality? II. An exhaustive survey of visual laterality studies from six neuropsychology journals","volume":"17","author":"M Hiscock","year":"1995","journal-title":"J Clin Exp Neuropsychol"},{"key":"pone.0309439.ref091","doi-asserted-by":"crossref","first-page":"4065","DOI":"10.1523\/JNEUROSCI.19-10-04065.1999","article-title":"Sex differences in brain gray and white matter in healthy young adults: correlations with cognitive performance","volume":"19","author":"RC Gur","year":"1999","journal-title":"J Neurosci"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0309439","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T17:34:49Z","timestamp":1729618489000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0309439"}},"subtitle":[],"editor":[{"given":"Nejat","family":"Mahdieh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,10,22]]},"references-count":91,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0309439","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,22]]}}}