{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:00:51Z","timestamp":1783548051562,"version":"3.55.0"},"reference-count":82,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>DNA\u2010directed RNA polymerase II subunit 3 (RPB3) is the third largest subunit of RNA polymerase II and is encoded by the <jats:italic>POLR2C<\/jats:italic> (OMIM:180663). A large Iranian family with congenital hearing loss and infertility is described here with genetic and clinical characterizations of five male patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>After doing clinical examinations, the proband was subjected to karyotyping and <jats:italic>GJB2\/6<\/jats:italic> sequencing to rule out the most evident chromosomal and gene abnormalities for male infertility and hearing loss, respectively. A custom\u2010designed next\u2010generation sequencing panel was also used to detect mutations in deafness\u2010related genes. Finally, to reveal the underlying molecular cause(s) justifying hearing loss and male infertility, five male patients and 2 healthy male controls within the family were subjected to paired\u2010end whole\u2010exome sequencing (WES). Linkage analysis was also performed based on the data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All male patients showed prelingual sensorineural hearing loss and also decreased sperm motility. Linkage analysis determined 16q21 as the most susceptible locus in which a missense variant in exon 7 of <jats:italic>POLR2C<\/jats:italic>\u2014NM_032940.3:c.545T&gt;C;p.(Val182Ala)\u2014was identified as a \u2018likely pathogenic\u2019 variant co\u2010segregated with phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Using segregation and in silico analyses, for the first time, we suggested that the NM_032940.3:c.545T&gt;C; p.(Val182Ala) in <jats:italic>POLR2C<\/jats:italic> is associated with hearing loss and male infertility.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.13946","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T14:20:57Z","timestamp":1672237257000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A biallelic variant in <scp>POLR2C<\/scp> is associated with congenital hearing loss and male infertility: Case report"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4489-2923","authenticated-orcid":false,"given":"Fatemeh","family":"Bitarafan","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Biology, North Tehran Branch Islamic Azad University  Tehran Iran"},{"name":"Department of Medical Genetics, DeNA Laboratory  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9926-3975","authenticated-orcid":false,"given":"Ehsan","family":"Razmara","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medical Sciences Tarbiat Modares University  Teheran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehsan","family":"Jafarinia","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medical Sciences Tarbiat Modares University  Teheran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navid","family":"Almadani","sequence":"additional","affiliation":[{"name":"Department of Genetics, Reproductive Biomedicine Research Center Royan Institute for Reproductive Biomedicine, ACECR  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoud","family":"Garshasbi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medical Sciences Tarbiat Modares University  Teheran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"issue":"3","key":"e_1_2_10_2_1","first-page":"333","article-title":"The first case of NSHL by direct impression on EYA1 gene and identification of one novel mutation in MYO7A in the Iranian families","volume":"21","author":"Razmara E","year":"2018","journal-title":"Iran J Basic Med Sci"},{"issue":"12","key":"e_1_2_10_3_1","article-title":"Novel homozygous variants in the TMC1 and CDH23 genes cause autosomal recessive nonsyndromic hearing loss. 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