{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:54:48Z","timestamp":1753890888744,"version":"3.41.2"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"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:sec><jats:title>Objective<\/jats:title><jats:p>To screen for possible pathogenic mutations in polycystic ovary syndrome (PCOS) patients with diabetes and preliminarily explore the relationship between genotype and phenotype to offer a research basis for PCOS pathogenesis with diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four patients with PCOS and diabetes were recruited and their demographic and clinical data were collected. Genomic DNA was extracted from peripheral blood leukocytes of the study subjects. High-throughput whole-exome sequencing was conducted to identify candidate genes that could play a pathogenic role in PCOS with diabetes in Aiji Taikang. The sequencing data obtained were evaluated using a variety of bioinformatics tools. Verification of candidate sites was done by Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Based on whole-exome sequencing, six mutations residing in three genes were detected in these four patients: (1) <jats:italic>MUC4<\/jats:italic> located at Chr 3q29, (2) FSHD region gene 1 (<jats:italic>FRG1<\/jats:italic>)gene located at Chr 4q35.2, and (3) androgen receptor (<jats:italic>AR<\/jats:italic>) located at Chr Xq11-q12 were detected in these four patients (every patients had the 6 mutations). Of the six genetic mutations, an insertion\/deletion (indel) mutation was found in the mucin 4 (<jats:italic>MUC4<\/jats:italic>) gene [MUC4:NM_018406.6:2\/25:c.7701_7702insTCAGTATCCACAGGTCATGCCACCCCTCTTCATGTCACCGACACTTCC:p.(Ser2567_Ala2568insSerValSerThrGlyHisAlaThrProLeuHisValThrAspThrSer)], and an indel mutation in the <jats:italic>AR<\/jats:italic> gene (<jats:italic>AR<\/jats:italic>:NM_000044:exon1:c.173_174insGCAGCA:p. Q58delinsQQQ), while the other four were missense single-nucleotide polymorphisms (SNPs) located in <jats:italic>FRG1<\/jats:italic> of uncertain significance (<jats:italic>FRG1<\/jats:italic>:NM_004477:exon8:c.T692C:p. L231P, <jats:italic>FRG1<\/jats:italic>:NM_004477:exon8:c.C728T:p.T243M, <jats:italic>FRG1<\/jats:italic>:NM_004477:exon8:c.C733A:p.L245M, FRG1:NM_004477:exon8:c.T734G:p.L245R). A Mucin 4 (<jats:italic>MUC4<\/jats:italic>) gene indel mutation was detected at the same site in four patients, which could be associated with endometriosis-related infertility. The <jats:italic>AR<\/jats:italic> gene indel mutation, <jats:italic>AR<\/jats:italic>:NM_000044:exon1:c.173_174insGCAGCA: p. Q58delinsQQQ was detected simultaneously in four patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Whole exome sequencing can quickly identify candidate genes for genes. Gaining an in-depth understanding of the AR mutations underlying PCOS with diabetes will deepen our understanding of the endocrine factors involved in the disease etiology, and provide potential targets for treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2025.1541946","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T05:29:16Z","timestamp":1747978156000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular variants of multiple genes were revealed by whole-exome sequencing in PCOS patients with diabetes"],"prefix":"10.3389","volume":"16","author":[{"given":"Chenglin","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"131495","DOI":"10.1016\/j.chemosphere.2021.131495","article-title":"The relationship between urinary phthalate metabolites and polycystic ovary syndrome in women undergoing in vitro fertilization: nested case-control study","volume":"286","author":"Al-Saleh","year":"2022","journal-title":"Chemosphere"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.3390\/genes13101906","article-title":"Genome-wide identification of potential mRNAs in drought response in wheat (Triticum aestivum L.)","volume":"13","author":"Aqeel","year":"2022","journal-title":"Genes"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/07391102.2024.2323141","article-title":"G-acp: a machine learning approach to the prediction of therapeutic peptides for gastric cancer","author":"Azad","year":"2024","journal-title":"J. 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