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To analyze the phenotypic features and pathogenic variants of three unrelated families presenting with nonsyndromic auditory neuropathy spectrum disorder (ANSD). <jats:italic>Methods<\/jats:italic>. Three recruited families that were affected by congenital deafness were clinically evaluated, including a detailed family history and audiological and radiological examination. The peripheral blood of all patients and their parents was collected for DNA extraction, and then, the exonic and flanking regions were enriched and sequenced using targeted capture and high\u2010throughput sequencing technology. Bioinformatics analyses and the Sanger sequencing were carried out to screen and validate candidate pathogenic variants. The pathogenicity of candidate variants was evaluated by an approach that was based on the standards and guidelines for interpreting genetic variants as proposed by the American College of Medical Genetics and Genomics (ACMG). <jats:italic>Results<\/jats:italic>. Four patients in three families were diagnosed as nonsyndromic ANSD, and all exhibited <jats:italic>OTOF<\/jats:italic> gene mutations. Among them, two individuals in family 1 (i.e., fam 1\u2010II\u20102 and fam 1\u2010II\u20103) carried homozygous variants c.[2688del];[2688del] (NM_194248.3). Two individuals from family 2 (fam 2\u2010II\u20101) and family 3 (fam 3\u2010II\u20104) carried compound heterozygous variants c.[4960G&gt;A];[1469C&gt;G] and c.[2675A&gt;G];[2977_2978del], respectively. <jats:italic>Conclusions<\/jats:italic>. Three unrelated pedigrees with ANSD were caused by pathogenic variants in the <jats:italic>OTOF<\/jats:italic> gene. Five mutations were found and included c.2688del, c.2675A&gt;G, c.2977_2978del, c.4960G&gt;A, and c.1469C&gt;G, of which the first two are novel and expanded mutational spectrum of the <jats:italic>OTOF<\/jats:italic> gene, thus having important implications for genetic counseling of the family.<\/jats:p>","DOI":"10.1155\/2020\/8843539","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T00:05:45Z","timestamp":1608681945000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Auditory Neuropathy Spectrum Disorder (ANSD)\u2014Clinical Characteristics and Pathogenic Variant Analysis of Three Nonsyndromic Deafness Families"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3173-3480","authenticated-orcid":false,"given":"Rongqun","family":"Zhai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9493-7333","authenticated-orcid":false,"given":"Haifeng","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingli","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6736-3004","authenticated-orcid":false,"given":"Danhua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongan","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanfei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxue","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7895-0899","authenticated-orcid":false,"given":"Hongen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9087-012X","authenticated-orcid":false,"given":"Bei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.260"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/119.3.741"},{"key":"e_1_2_10_3_2","first-page":"323","article-title":"Auditory neuropathy and inner hair cell and synapses","volume":"43","author":"Starr A.","year":"2008","journal-title":"Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1515\/jbcpp.2000.11.3.215"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003446-200010000-00012"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2010.11.023"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.2741\/3984"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/7693"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/303049"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.08.040"},{"key":"e_1_2_10_11_2","article-title":"Disruption of otoferlin alters the mode of exocytosis at the mouse inner hair cell ribbon synapse","volume":"11","author":"Takago H.","year":"2018","journal-title":"Frontiers in Molecular Neuroscience"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.31013"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1550-18.2018"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-009-8058-z"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2005.09.006"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.1.45"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10274"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1445"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_10_20_2","unstructured":"LiH. 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