{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:45:55Z","timestamp":1790095555648,"version":"4.0.1"},"reference-count":128,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["469177153"],"award-info":[{"award-number":["469177153"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hearing loss is a clinically and genetically heterogeneous disorder, with over 148 genes and 170 loci associated with its pathogenesis. The spectrum and frequency of causal variants vary across different genetic ancestries and are more prevalent in populations that practice consanguineous marriages. Pakistan has a rich history of autosomal recessive gene discovery related to non\u2010syndromic hearing loss. Since the first linkage analysis with a Pakistani family that led to the mapping of the DFNB1 locus on chromosome 13, 51 genes associated with this disorder have been identified in this population. Among these, 13 of the most prevalent genes, namely <jats:italic>CDH23<\/jats:italic>, <jats:italic>CIB2<\/jats:italic>, <jats:italic>CLDN14<\/jats:italic>, <jats:italic>GJB2<\/jats:italic>, <jats:italic>HGF<\/jats:italic>, <jats:italic>MARVELD2<\/jats:italic>, <jats:italic>MYO7A<\/jats:italic>, <jats:italic>MYO15A<\/jats:italic>, <jats:italic>MSRB3<\/jats:italic>, <jats:italic>OTOF<\/jats:italic>, <jats:italic>SLC26A4<\/jats:italic>, <jats:italic>TMC1<\/jats:italic> and <jats:italic>TMPRSS3<\/jats:italic>, account for more than half of all cases of profound hearing loss, while the prevalence of other genes is less than 2% individually. In this review, we discuss the most common autosomal recessive non\u2010syndromic hearing loss genes in Pakistani individuals as well as the genetic mapping and sequencing approaches used to discover them. Furthermore, we identified enriched gene ontology terms and common pathways involved in these 51 autosomal recessive non\u2010syndromic hearing loss genes to gain a better understanding of the underlying mechanisms. Establishing a molecular understanding of the disorder may aid in reducing its future prevalence by enabling timely diagnostics and genetic counselling, leading to more effective clinical management and treatments of hearing loss.<\/jats:p>","DOI":"10.1111\/jcmm.18119","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T13:34:25Z","timestamp":1711546465000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Autosomal recessive non\u2010syndromic hearing loss genes in Pakistan during the previous three decades"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6043-6811","authenticated-orcid":false,"given":"Madiha","family":"Shadab","sequence":"first","affiliation":[{"name":"Department of Zoology Mirpur University of Science and Technology  Mirpur Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8140-0756","authenticated-orcid":false,"given":"Ansar Ahmed","family":"Abbasi","sequence":"additional","affiliation":[{"name":"Department of Zoology Mirpur University of Science and Technology  Mirpur Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9679-6327","authenticated-orcid":false,"given":"Ahsan","family":"Ejaz","sequence":"additional","affiliation":[{"name":"Department of Physics University of Kotli Azad Jammu and Kashmir  Kotli Pakistan"},{"name":"School of Nuclear Science and Technology Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3520-8015","authenticated-orcid":false,"given":"Afif","family":"Ben\u2010Mahmoud","sequence":"additional","affiliation":[{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3613-6378","authenticated-orcid":false,"given":"Vijay","family":"Gupta","sequence":"additional","affiliation":[{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4497-4686","authenticated-orcid":false,"given":"Hyung\u2010Goo","family":"Kim","sequence":"additional","affiliation":[{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University  Doha Qatar"},{"name":"College of Health &amp; Life Sciences Hamad Bin Khalifa University (HBKU)  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6719-3447","authenticated-orcid":false,"given":"Barbara","family":"Vona","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"},{"name":"Institute for Auditory Neuroscience and Inner Ear Lab University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,27]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-021-02320-0"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-021-02335-7"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12339"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0022215113003265"},{"issue":"3","key":"e_1_2_12_6_1","first-page":"17","article-title":"Cranial nerve VIII: hearing and vestibular functions","volume":"7","author":"Sanders RD","year":"2010","journal-title":"Psychiatry"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-015-3838-8"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100146"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000091090"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0511(02)00052-2"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1995.tb01610.x"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2884728"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181ceb95d"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/387080a0"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390100604"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(01)00200-8"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/342193"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng842"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-002-0732-4"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg358"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.5.360"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.4.242"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1086\/375122"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-5-24"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.018523"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2006.00613.x"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1086\/499164"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1086\/510022"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.039834"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-006-0275-1"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.09.008"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.245"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2008.01128.x"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.06.003"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.07.003"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.01.030"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.12.017"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.11.010"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-011-1018-5"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.12.011"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2012.05.013"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2426"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599813493075"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.05.018"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12047"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003774"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22545"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.12.004"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu042"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005097"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103023"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.12.004"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2016.0328"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-017-0582-8"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007297"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI97350"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-019-0691-4"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-020-01087-x"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-020-06037-7"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5584788"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0268078"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac257"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-022-01391-w"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2013.114"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcp.2015.03.008"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-021-02359-z"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23666"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11111329"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2008.06.004"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11121474"},{"key":"e_1_2_12_72_1","first-page":"1843","article-title":"Expression of cadherin 23 isoforms is not conserved: implications for a mouse model of usher syndrome type 1D","volume":"15","author":"Lagziel A","year":"2009","journal-title":"Mol Vis"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/83667"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-022-02431-2"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1086\/316954"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100262"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708087"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00401"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073552"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13170"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20184579"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1177\/0003489415575549"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60405"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg210"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12856"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2010.104"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1001\/archoto.2009.202"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/30639"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800793105"},{"key":"e_1_2_12_90_1","volume-title":"Connexin Methods and Protocols","author":"Bruzzone R","year":"2001"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2005.00379.x"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0259083"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-016-1648-8"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2278-19.2020"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a002584"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-015-1532-y"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69031"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2021.04.005"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a021931"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2022.102132"},{"key":"e_1_2_12_101_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15936-z"},{"key":"e_1_2_12_102_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr155"},{"key":"e_1_2_12_103_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9404"},{"key":"e_1_2_12_104_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1219"},{"key":"e_1_2_12_105_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-17757-0"},{"key":"e_1_2_12_106_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-019-0790-2"},{"key":"e_1_2_12_107_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt549"},{"key":"e_1_2_12_108_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2578"},{"key":"e_1_2_12_109_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.162099"},{"key":"e_1_2_12_110_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2016.10"},{"key":"e_1_2_12_111_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11121411"},{"key":"e_1_2_12_112_1","doi-asserted-by":"publisher","DOI":"10.1038\/7693"},{"key":"e_1_2_12_113_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10274"},{"key":"e_1_2_12_114_1","doi-asserted-by":"publisher","DOI":"10.1159\/000335119"},{"key":"e_1_2_12_115_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201611"},{"key":"e_1_2_12_116_1","volume-title":"StatPearls","author":"Garabet Diramerian L","year":"2022"},{"key":"e_1_2_12_117_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2009.21"},{"key":"e_1_2_12_118_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2210849119"},{"key":"e_1_2_12_119_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.16041"},{"key":"e_1_2_12_120_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.07.033"},{"key":"e_1_2_12_121_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anl.2014.04.001"},{"key":"e_1_2_12_122_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2007.00895.x"},{"key":"e_1_2_12_123_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-018-2793-2"},{"key":"e_1_2_12_124_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2022-108654"},{"key":"e_1_2_12_125_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.23.2829"},{"key":"e_1_2_12_126_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds532"},{"key":"e_1_2_12_127_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-011-0282-3"},{"key":"e_1_2_12_128_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01695.x"},{"key":"e_1_2_12_129_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2023.147335"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.18119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T04:47:05Z","timestamp":1714193225000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.18119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,27]]},"references-count":128,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1111\/jcmm.18119"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.18119","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,27]]},"assertion":[{"value":"2023-06-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e18119"}}