{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T21:16:26Z","timestamp":1775855786849,"version":"3.50.1"},"reference-count":92,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T00:00:00Z","timestamp":1647302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Male infertility is a disorder of the reproductive system with a highly complex genetic landscape. In most cases, the reason for male infertility remains unknown; however, the importance of genetic abnormalities in the diagnosis of subfertility\/infertility is becoming increasingly recognized. Several syndromes include impaired male fertility in the clinical picture, although a comprehensive analysis of genetic causes of the syndromology perspective of male reproduction is not yet available.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>(1) To develop a catalog of syndromes and corresponding genes associated with impaired male fertility and (2) to visualize an up\u2010to\u2010date genome\u2013phenome network of syndromic male subfertility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Published literature was retrieved from the Online Mendelian Inheritance in Man, Orphanet, Human Phenotype Ontology and PubMed databases using keywords \u201cmale infertility,\u201d \u201csyndrome,\u201d \u201cgene,\u201d and \u201ccase report\u201d; time period from 1980 to September, 2021. Retrieved data were organized as a catalog and complemented with identification numbers of syndromes (MIM ID) and genes (Gene ID). The genome\u2013phenome network and the phenome network were visualized using Cytoscape and Gephi software platforms. Protein\u2013protein interaction analysis was performed using STRING tool.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Retrieved syndromes were presented as (1) a catalog containing 63 syndromes and 93 associated genes, (2) a genome\u2013phenome network including <jats:italic>CHD7<\/jats:italic> and <jats:italic>WT1<\/jats:italic> genes and Noonan and Kartagener syndromes, and (3) a phenome network including 63 syndromes, and 25 categories of clinical features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The developed catalog will contribute to the advances and translational impact toward understanding the factors of syndromic male infertility. Visualized networks provide simple, flexible tools for clinicians and researchers to quickly generate hypotheses and gain a deeper understanding of underlying mechanisms affecting male reproduction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Recognition of the significance of genome\u2013phenome visualization as part of network medicine can help expedite efforts toward unravelling molecular mechanisms and enable advances personal\/precision medicine of male reproduction and other complex traits.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13167","type":"journal-article","created":{"date-parts":[[2022,2,26]],"date-time":"2022-02-26T02:22:58Z","timestamp":1645842178000},"page":"720-732","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Syndromic male subfertility: A network view of genome\u2013phenome associations"],"prefix":"10.1111","volume":"10","author":[{"given":"\u0160pela","family":"Mikec","sequence":"first","affiliation":[{"name":"Department of Animal Science, Biotechnical Faculty University of Ljubljana  Dom\u017eale Slovenia 1230"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u017diva","family":"Kolenc","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Biotechnical Faculty University of Ljubljana  Dom\u017eale Slovenia 1230"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Borut","family":"Peterlin","sequence":"additional","affiliation":[{"name":"Clinical Institute for Genomic Medicine University Medical Center Ljubljana  \u0160lajmerjeva 4 Ljubljana Slovenia 1000"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Horvat","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Biotechnical Faculty University of Ljubljana  Dom\u017eale Slovenia 1230"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ne\u017ea","family":"Pogorevc","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Biotechnical Faculty University of Ljubljana  Dom\u017eale Slovenia 1230"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0465-1762","authenticated-orcid":false,"given":"Tanja","family":"Kunej","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Biotechnical Faculty University of Ljubljana  Dom\u017eale Slovenia 1230"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2018.1453358"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.103.026880"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12198"},{"key":"e_1_2_8_5_1","unstructured":"RowePJ ComhaireFH HargreaveTB MahmoudAMA OrganizationWH.WHO manual for the standardized investigation diagnosis and management of the infertile male. Cambridge University Press."},{"key":"e_1_2_8_6_1","author":"Jungwirth A","year":"2015","journal-title":"EAU Guidelines on Male Infertility"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/19396368.2016.1250181"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/3.5.419"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585\u2010018\u20100003\u20103"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dez022"},{"issue":"7","key":"e_1_2_8_11_1","first-page":"645","article-title":"Blough RI. 45,X\/46,X,r(Y) karyotype transmitted by father to son after intracytoplasmic sperm injection for oligospermia. A case report","volume":"44","author":"Bofinger MK","year":"1999","journal-title":"J Reprod Med"},{"issue":"1","key":"e_1_2_8_12_1","first-page":"24","article-title":"Rare syndromes associated with infertility","volume":"6","author":"Hempel M","year":"2009","journal-title":"J fur Reproduktionsmedizin Endokrinol"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-4017-7_8"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439\u20100531.2010.01648.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00425"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmab030"},{"key":"e_1_2_8_17_1","unstructured":"\u201cPrevalence of Rare Diseases: Bibliographic Data\u201d Orphanet Report Series Rare Diseases Collection January 2021 Number 1: Diseases Listed in Alphabetical Order.https:\/\/www.orpha.net\/orphacom\/cahiers\/docs\/GB\/Prevalence_of_rare_diseases_by_alphabetical_list.pdf."},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1205"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1105"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1071"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bar030"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz966"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx346"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_8_26_1","unstructured":"BastianM HeymannS JacomyM.Gephi: an open source software for exploring and manipulating networks. In:International AAAI Conference on Weblogs and Social Medi San Jose CA 17\u201020 May2009.http:\/\/www.aaai.org\/ocs\/index.php\/ICWSM\/09\/paper\/view\/154."},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096\u20108628(19961218)66"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43653"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.130"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010018\u20100121\u20107"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw282"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2005.06.043"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.4067\/S0034\u201098872011000800012"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13001"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem\u201045\u20102\u2010240"},{"issue":"4","key":"e_1_2_8_36_1","first-page":"357","article-title":"Effect of gonadotrophins, testosterone and growth hormone on spermatogenesis in two hypophysectomy patients","volume":"24","author":"Martin\u2010Du Pan RC","year":"1995","journal-title":"J Gynecol Obstet Biol Reprod"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u20105347(17)59651\u20102"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.045765"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.107.003731"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey377"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx440"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.1.02293"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1086\/319511"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.25.5.4619"},{"key":"e_1_2_8_45_1","unstructured":"YzerS I den HollanderA LopezI et\u00a0al.Ocular and extra\u2010ocular features of patients with Leber congenital amaurosis and mutations in CEP290. 2018.https:\/\/pubmed.ncbi.nlm.nih.gov\/22355252\/. Accessed September 24 2021."},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1324025111"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2012.03.005"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011\u20101493"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38230"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dms050"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881\u2010018\u20100693\u20107"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.10.001"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07471"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.01.011"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.726"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102012\u2010100867"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/crj.12268"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00023"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815\u2010015\u20100474\u20106"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.08.022"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/aja.2013.65"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.10.003"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028223"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1854269"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2707"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201008510\u2010z"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.05.004"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23005"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.06.022"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.11.019"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14279"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2014.10.006"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.11.009"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.03.003"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2007.03.005"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007\u20101656"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013060651"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2014.389"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1080\/13506129.2018.1438390"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1159\/000323441"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.4274\/Jcrpe.1098"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1590\/s0104\u201042302000000100014"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.12549"},{"key":"e_1_2_8_84_1","first-page":"37","article-title":"Studies bearing on fertility of male and female mongoloids","volume":"65","author":"Stearns PE","year":"1960","journal-title":"Am J Ment Defic"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439\u20100272.2010.01129.x"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpuro0775"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30097"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2016.06.041"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.5534\/wjmh.180055"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102265.2007.03069.x"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2014.05.005"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2012.04.048"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.107.003699"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.13167","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/andr.13167","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.13167","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T12:54:30Z","timestamp":1692536070000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.13167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,15]]},"references-count":92,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1111\/andr.13167"],"URL":"https:\/\/doi.org\/10.1111\/andr.13167","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,15]]},"assertion":[{"value":"2020-08-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}