{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:31:35Z","timestamp":1770139895477,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"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":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Isolated congenital bilateral absence of vas deferens (iCBAVD) in men results in obstructive azoospermia and is mainly caused by pathogenic variants in cystic fibrosis transmembrane conductance regulator (<jats:italic>CFTR<\/jats:italic>) or adhesion G protein\u2010coupled receptor G2 (<jats:italic>ADGRG2<\/jats:italic>)<jats:italic>.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The next\u2010generation sequencing (NGS) was used to screen the mutations in the proband, and Sanger sequencings were performed to validate the compound heterozygous variant of <jats:italic>CFTR<\/jats:italic> in his family members<jats:italic>.<\/jats:italic> Protein structure simulation was performed to discover the potential pathological mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This study reported novel compound heterozygous <jats:italic>CFTR<\/jats:italic> mutations (NM:000492.4, Intron: 5T; c.3965_3969dupTTGGG: p.R1325Gfs*5) in two brothers with obstructive azoospermia. The compound heterozygous <jats:italic>CFTR<\/jats:italic> mutations were first screened out by NGS in an infertile male patient who exhibited iCBAVD from a nonconsanguineous Chinese family. Histological analysis of the testicular biopsy from this patient revealed normal spermatogenesis and mature spermatozoa were observed in the seminiferous tubules. Surprisingly, the same compound heterozygous <jats:italic>CFTR<\/jats:italic> mutations were also observed in his brothers who also exhibited iCBAVD, with their parents being a heterozygous carrier for the mutations, as verified by Sanger sequencing. Protein structure simulation revealed that these mutations potentially led to impaired ATP\u2010binding ability of CFTR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identified novel compound heterozygous <jats:italic>CFTR<\/jats:italic> mutations in two brothers and summarized the literature regarding <jats:italic>CFTR<\/jats:italic> mutation and male infertility. Our study may contribute to the genetic diagnosis of iCBAVD and future genetic counseling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2249","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T06:50:48Z","timestamp":1690267848000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Compound heterozygous variants in <i>CFTR<\/i> with potentially reducing <scp>ATP<\/scp>\u2010binding ability identified in Chinese infertile brothers with isolated congenital bilateral absence of vas deferens"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0704-7210","authenticated-orcid":false,"given":"Shi","family":"Shengjia","sequence":"first","affiliation":[{"name":"Reproductive Center Northwest Women's and Children's Hospital  Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Lei","sequence":"additional","affiliation":[{"name":"Reproductive Center Northwest Women's and Children's Hospital  Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Tianwei","sequence":"additional","affiliation":[{"name":"Reproductive Center Northwest Women's and Children's Hospital  Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Hongmei","sequence":"additional","affiliation":[{"name":"School of Medicine Southeast University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi","family":"Juanzi","sequence":"additional","affiliation":[{"name":"Reproductive Center Northwest Women's and Children's Hospital  Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiao","family":"Sen","sequence":"additional","affiliation":[{"name":"Reproductive Center Northwest Women's and Children's Hospital  Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,7,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0929\u2010693X(20)30044\u20100"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.775123"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10235538"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815\u2010022\u201002417\u2010z"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0293\u2010151"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22063264"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1472\u20106483(10)60801\u20102"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00007.2018"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI639"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12925"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201065287\u20104"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04712"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijmr.IJMR_906_18"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815\u2010019\u201001617\u20104"},{"issue":"4","key":"e_1_2_13_17_1","first-page":"315","article-title":"Exon 10 CFTR gene mutation in male infertility","volume":"10","author":"Hojati Z.","year":"2012","journal-title":"Iranian Journal of Reproductive Medicine"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.1925"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201711946"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.02.024"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032\u2010022\u201000885\u20103"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13256\u2010022\u201003399\u20103"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6507583"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0242094"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.3233\/DMA\u20102011\u20100880"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12769"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh073"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der377"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684\u2010021\u20100846\u20105"}],"container-title":["Molecular Genetics &amp; 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