{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:48:48Z","timestamp":1790768928770,"version":"4.1.0"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Primary ciliary dyskinesia (PCD) is a clinically and genetically heterogeneous ciliopathy affecting the cilia and sperm flagella. Mutations in genes related to the structural and functional defects of respiratory ciliary axoneme have been reported to be the predominant cause of this symptom; however, evidence regarding male infertility and genotype\u2013phenotype associations between some of these genes and flagellar axoneme remains unclear. Here, we reported a male patient from a non-consanguineous Chinese family who exhibited left\/right body asymmetry and oligoasthenoterazoospermia factor infertility. Novel compound heterozygous mutations in <jats:italic>ARMC4<\/jats:italic> (NM:018076: c.2095C&amp;gt;T: p. Gln699<jats:sup>*<\/jats:sup>; c.1679C&amp;gt;T: p. Ala560Val) were identified in this patient, and his parents were a heterozygous carrier for the mutations. Morphological and ultrastructural analysis of the spermatozoa from the man showed aberrant sperm flagella with axonemal disorganization and outer dynein arm (ODA) loss. In addition, immunofluorescence analysis of the spermatozoa from the proband and a control man revealed a significant lower expression of ARMC4 protein due to pathogenic mutations. Therefore, our findings help to expand the spectrum of <jats:italic>ARMC4<\/jats:italic> pathogenic mutations and linked biallelic <jats:italic>ARMC4<\/jats:italic> mutations to male infertility for the first time.<\/jats:p>","DOI":"10.3389\/fgene.2021.715339","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T08:41:57Z","timestamp":1627634517000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Case Report: Novel Biallelic Mutations in ARMC4 Cause Primary Ciliary Dyskinesia and Male Infertility in a Chinese Family"],"prefix":"10.3389","volume":"12","author":[{"given":"Yang","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qunshan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingrong","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuokuo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaolian","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangbiao","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1093\/humrep\/dev251","article-title":"Another look at human sperm morphology","volume":"31","author":"Auger","year":"2016","journal-title":"Hum. Reprod."},{"key":"B2","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.gene.2013.08.080","article-title":"Gudu, an Armadillo repeat-containing protein, is required for spermatogenesis in Drosophila","volume":"531","author":"Cheng","year":"2013","journal-title":"Gene"},{"key":"B3","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/S0962-8924(03)00167-3","article-title":"Armadillo repeat proteins: beyond the animal kingdom","volume":"13","author":"Coates","year":"2003","journal-title":"Trends Cell Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1093\/humupd\/dmp048","article-title":"World Health Organization reference values for human semen characteristics","volume":"16","author":"Cooper","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"B5","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/nrm2278","article-title":"When cilia go bad: cilia defects and ciliopathies","volume":"8","author":"Fliegauf","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1183\/13993003.00736-2016","article-title":"Clinical manifestations in primary ciliary dyskinesia: systematic review and meta-analysis","volume":"48","author":"Goutaki","year":"2016","journal-title":"Eur. Respir. J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"157.e5","DOI":"10.1016\/j.jpeds.2020.05.052","article-title":"Clinical and genetic spectrum of children with primary ciliary dyskinesia in China","volume":"225","author":"Guo","year":"2020","journal-title":"J. Pediatr"},{"key":"B8","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.ajhg.2020.07.010","article-title":"Bi-allelic loss-of-function variants in CFAP58 cause flagellar axoneme and mitochondrial sheath defects and asthenoteratozoospermia in humans and mice","volume":"107","author":"He","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.ajhg.2013.06.009","article-title":"ARMC4 mutations cause primary ciliary dyskinesia with randomization of left\/right body asymmetry","volume":"93","author":"Hjeij","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"204.e5","DOI":"10.1016\/j.urology.2006.01.072","article-title":"Obstructive azoospermia associated with chronic sinopulmonary infection and situs inversus totalis","volume":"68","author":"Ichioka","year":"2006","journal-title":"Urology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1093\/biolre\/iox096","article-title":"Formation and function of sperm tail structures in association with sperm motility defects","volume":"97","author":"Lehti","year":"2017","journal-title":"Biol. Reprod."},{"key":"B12","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/S2213-2600(19)30374-1","article-title":"Primary ciliary dyskinesia in the genomics age","volume":"8","author":"Lucas","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.fertnstert.2011.11.003","article-title":"Normal live birth after testicular sperm extraction and intracytoplasmic sperm injection in variant primary ciliary dyskinesia with completely immotile sperm and structurally abnormal sperm tails","volume":"97","author":"McLachlan","year":"2012","journal-title":"Fertil. Steril."},{"key":"B14","doi-asserted-by":"publisher","first-page":"135","DOI":"10.3389\/fped.2017.00135","article-title":"Primary ciliary dyskinesia: an update on clinical aspects, genetics, diagnosis, and future treatment strategies","volume":"5","author":"Mirra","year":"2017","journal-title":"Front Pediatr"},{"key":"B15","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1136\/jmedgenet-2013-101938","article-title":"Combined exome and whole-genome sequencing identifies mutations in ARMC4 as a cause of primary ciliary dyskinesia with defects in the outer dynein arm","volume":"51","author":"Onoufriadis","year":"2014","journal-title":"J. Med. Genet."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03389-7","article-title":"Sperm defects in primary ciliary dyskinesia and related causes of male infertility","author":"Sironen","year":"2019","journal-title":"Cell. Mol. Life Sci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-020-02113-x","article-title":"The genetic architecture of morphological abnormalities of the sperm tail","author":"Toure","year":"2020","journal-title":"Hum. Genet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/s00404-008-0671-y","article-title":"Can pentoxifylline improve the sperm motion and ICSI success in the primary ciliary dyskinesia?","volume":"279","author":"Yildirim","year":"2009","journal-title":"Arch. Gynecol. Obstet."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.715339\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T08:42:00Z","timestamp":1627634520000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.715339\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,30]]},"references-count":18,"alternative-id":["10.3389\/fgene.2021.715339"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2021.715339","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,30]]},"article-number":"715339"}}