{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:18:36Z","timestamp":1792426716628,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T00:00:00Z","timestamp":1577318400000},"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":["Andrology"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital absence of vas deferens (CAVD) represents a major cause of obstructive azoospermia and is mainly related to biallelic alteration of the <jats:italic>CFTR<\/jats:italic> gene, also involved in cystic fibrosis. Using whole exome sequencing, we recently identified hemizygous loss\u2010of\u2010function mutations in the Adhesion G Protein\u2010coupled Receptor G2 gene (<jats:italic>ADGRG2<\/jats:italic>) as responsible of isolated CAVD in the absence of associated unilateral renal agenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The objective of this study was to retrospectively perform <jats:italic>ADGRG2<\/jats:italic> sequencing on a large cohort of patients with CAVD, and 0 or only 1 <jats:italic>CFTR<\/jats:italic> defective allele identified after comprehensive testing in order to (a) define more precisely the spectrum and the frequency of <jats:italic>ADGRG2<\/jats:italic> mutations within Caucasian population (b) explore the possibility of co\u2010occurrence of <jats:italic>CFTR<\/jats:italic> and <jats:italic>ADGRG2<\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>We collected 53 DNA samples from CAVD patients with 0 (n\u00a0=\u00a023) or 1 (n\u00a0=\u00a030) alteration identified after comprehensive <jats:italic>CFTR<\/jats:italic> testing in order to perform <jats:italic>ADGRG2<\/jats:italic> sequencing. Twenty patients had normal ultrasonographic renal examination, and renal status was not documented for 33 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified six new truncating <jats:italic>ADGRG2<\/jats:italic> mutations in 8 patients including two twin brothers: c.251C\u00a0&gt;\u00a0G (p.Ser84*), c.1013delC (p.Pro338Hisfs*4), c.1460delG (p.Gly487Alafs*9), c.2096dupT (p.Phe700Ilefs*29), c.2473C\u00a0&gt;\u00a0T (p.Arg825*), and c.1731_1839\u00a0+\u00a0373del (p.Asn578Thrfs*12), which is a 596 base pair deletion affecting the last five bases of exon 21 and the whole exon 22. Five of the eight patients also harbored an heterozygous <jats:italic>CFTR<\/jats:italic> mutation which we consider as incidental regarding the high penetrance expected for <jats:italic>ADGRG2<\/jats:italic> truncating variants. The frequency of <jats:italic>ADGRG2<\/jats:italic> truncating mutation was 26% (5\/19 unrelated patients) when presence of both kidneys was attested by ultrasonography and 6.1% (2\/33) among patients with unknown renal status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion &amp; Conclusion<\/jats:title><jats:p>Our results confirm the interest of <jats:italic>ADGRG2<\/jats:italic> sequencing in patients with CAVD not formerly related to CFTR dysfunction, especially in the absence of associated unilateral renal agenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.12744","type":"journal-article","created":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T09:38:00Z","timestamp":1576575480000},"page":"618-624","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Novel ADGRG2 truncating variants in patients with X\u2010linked congenital absence of vas deferens"],"prefix":"10.1111","volume":"8","author":[{"given":"Adrien","family":"Pagin","sequence":"first","affiliation":[{"name":"CHU Lille Service de Toxicologie et G\u00e9nopathies Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Bergougnoux","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire Centre Hospitalier Universitaire de Montpellier EA7402 Laboratoire de G\u00e9n\u00e9tique de Maladies Rares Universit\u00e9 de Montpellier Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Girodon","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires AP\u2010HP.5 Groupe Hospitalier HUPC Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Pierre","family":"Reboul","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale Centre Hospitalier R\u00e9gional Universitaire Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Willoquaux","sequence":"additional","affiliation":[{"name":"CHU Lille Service de Toxicologie et G\u00e9nopathies Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryse","family":"Kesteloot","sequence":"additional","affiliation":[{"name":"CHU Lille Service de Toxicologie et G\u00e9nopathies Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Raynal","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire Centre Hospitalier Universitaire de Montpellier EA7402 Laboratoire de G\u00e9n\u00e9tique de Maladies Rares Universit\u00e9 de Montpellier Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Bienvenu","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique et Biologie Mol\u00e9culaires AP\u2010HP.5 Groupe Hospitalier HUPC Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Humbert","sequence":"additional","affiliation":[{"name":"Service de Biologie de la Reproduction Centre Hospitalier R\u00e9gional Universitaire Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Lalau","sequence":"additional","affiliation":[{"name":"CHU Lille Service de Toxicologie et G\u00e9nopathies Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Bieth","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale Centre Hospitalier Universitaire Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)90292-5"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2007.070040"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2018.10.012"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1569-1993(11)60014-3"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2008.03.009"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200008)16:2<143::AID-HUMU7>3.0.CO;2-J"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1472-6483(10)60801-2"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23276"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(00)01625-3"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.19.8642-8648.2004"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)92066-Q"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2008.03.007"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)64278-2"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-34262-5"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty897"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.86"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12019"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/16.2.282"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.10220"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.06.012"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu703"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dem024"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18162"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-101713"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0810-575"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/den500"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1439-0272.2000.00327.x"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20892"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ucl.2013.08.013"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der377"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12592"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.33432"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fandr.12744","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.12744","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/andr.12744","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.12744","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T06:41:51Z","timestamp":1693896111000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.12744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,26]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1111\/andr.12744"],"URL":"https:\/\/doi.org\/10.1111\/andr.12744","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,26]]},"assertion":[{"value":"2019-08-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}