BMC Medical Genomics最新文献

{"title":"Analysis of prenatal diagnosis and pregnancy outcomes for rare autosomal trisomies detected by non-invasive prenatal testing in 33,079 cases.","authors":"Xu Yan, Kai Ding, Xin Zhang, Shuai Zhang, Haiying Peng, Ying Zhang","doi":"10.1186/s12920-025-02099-3","DOIUrl":"10.1186/s12920-025-02099-3","url":null,"abstract":"<p><strong>Background: </strong>Non-invasive prenatal testing is widely used for screening common fetal aneuploidy disorders such as trisomy 21, trisomy 18, and trisomy 13. However, its ability to detect rare autosomal trisomies has introduced a new layer of complexity and clinical uncertainty.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on the prenatal diagnostic results and pregnancy outcomes of cases identified as high-risk for rare autosomal trisomies through non-invasive prenatal testing at the reproductive medicine center, Renmin hospital, Hubei university of medicine, from 2015 to 2023.</p><p><strong>Results: </strong>66 cases identified as high-risk for rare autosomeal trisomies, yielding a detection rate of 0.20% (66/33,079). 7 declined amniocentesis, while the others underwent the procedure. Prenatal diagnostic procedures did not confirm the presence of the corresponding rare autosomal trisomy in any of these cases. Among the 66 cases of rare autosomal trisomies (RATs), 5 cases were lost to follow-up, and 1 case underwent termination of pregnancy (TOP) for personal reasons, leaving 60 cases with valid pregnancy outcomes. Of these 60 valid outcomes, 50 (83.33%) resulted in full-term births, while 10 (16.67%) experienced adverse pregnancy outcomes.</p><p><strong>Conclusion: </strong>Prenatal diagnosis for high-risk rare autosomal trisomies typically reveals a normal karyotype with no detectable chromosomal abnormalities, and most cases can achieve full-term pregnancy outcomes. However, adverse pregnancy outcomes such as preterm birth, fetal demise, placental abnormalities, and intrauterine growth restriction are common and should be given clinical attention and consideration.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"29"},"PeriodicalIF":2.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating microRNA panels for multi-cancer detection and gastric cancer screening: leveraging a network biology approach.","authors":"Leila Kamkar, Samaneh Saberi, Mehdi Totonchi, Kaveh Kavousi","doi":"10.1186/s12920-025-02091-x","DOIUrl":"10.1186/s12920-025-02091-x","url":null,"abstract":"<p><strong>Background: </strong>Screening tests, particularly liquid biopsy with circulating miRNAs, hold significant potential for non-invasive cancer detection before symptoms manifest.</p><p><strong>Methods: </strong>This study aimed to identify biomarkers with high sensitivity and specificity for multiple and specific cancer screening. 972 Serum miRNA profiles were compared across thirteen cancer types and healthy individuals using weighted miRNA co-expression network analysis. To prioritize miRNAs, module membership measure and miRNA trait significance were employed. Subsequently, for specific cancer screening, gastric cancer was focused on, using a similar strategy and a further step of preservation analysis. Machine learning techniques were then applied to evaluate two distinct miRNA panels: one for multi-cancer screening and another for gastric cancer classification.</p><p><strong>Results: </strong>The first panel (hsa-miR-8073, hsa-miR-614, hsa-miR-548ah-5p, hsa-miR-1258) achieved 96.1% accuracy, 96% specificity, and 98.6% sensitivity in multi-cancer screening. The second panel (hsa-miR-1228-5p, hsa-miR-1343-3p, hsa-miR-6765-5p, hsa-miR-6787-5p) showed promise in detecting gastric cancer with 87% accuracy, 90% specificity, and 89% sensitivity.</p><p><strong>Conclusions: </strong>Both panels exhibit potential for patient classification in diagnostic and prognostic applications, highlighting the significance of liquid biopsy in advancing cancer screening methodologies.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"27"},"PeriodicalIF":2.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pathogenic COL7A1 variant highlights semi-dominant inheritance in dystrophic epidermolysis bullosa.","authors":"Saira Sattar, Thashi Bharadwaj, Umm-E- Kalsoom, Anushree Acharya, Saadullah Khan, Suzanne M Leal, Isabelle Schrauwen","doi":"10.1186/s12920-024-02077-1","DOIUrl":"10.1186/s12920-024-02077-1","url":null,"abstract":"<p><p>Dystrophic epidermolysis bullosa is a rare subtype of inherited epidermolysis bullosa, caused by variants in the collagen type VII alpha 1 chain (COL7A1) gene (MIM120120). Both autosomal dominant and recessive inheritance has been reported with variable phenotype. We investigated a Pakistani family with dystrophic epidermolysis bullosa via exome sequencing and identified a pathogenic nonsense variant in COL7A1 NM_000094 c.1573 C > T:p.(Arg525*). The inheritance pattern observed was consistent with a semi-dominant model, where heterozygous parents exhibited a mild phenotype, and homozygous children were more severely affected. For dystrophic epidermolysis bullosa, loss-of-function variants are typically associated with the autosomal recessive form, while missense variants are linked to the autosomal dominant form. A review of the literature suggests a semi-dominance pattern for some missense variants, particularly glycine substitutions, but this concept had not been formally recognized. This study highlights the importance of considering semi-dominant inheritance models for dystrophic epidermolysis bullosa and other Mendelian diseases with an autosomal recessive mode of inheritance, as it can significantly impact diagnosis and genetic counseling.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"26"},"PeriodicalIF":2.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Hypercalcemia and co-occurring TBX1 mutation in Glycogen Storage Disease Type Ib: case report.","authors":"Zakaria Kasmi, Imane Ain El Hayat, Zahra Aadam, Abderrahmane Errami, Ibtihal Benhsaien, Jalila El Bakkouri, Dalal Ben Sabbahia, Meryem Atrassi, Ahmed Aziz Bousfiha, Fatima Ailal","doi":"10.1186/s12920-025-02095-7","DOIUrl":"10.1186/s12920-025-02095-7","url":null,"abstract":"","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"25"},"PeriodicalIF":2.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between mucin gene polymorphisms and different types of gallbladder stones.","authors":"Gongqing Ren, Yongmao Fan, Ruizi Zhong, Gang Zou, Xiaojun Huang, Yue Zhang","doi":"10.1186/s12920-025-02090-y","DOIUrl":"10.1186/s12920-025-02090-y","url":null,"abstract":"<p><strong>Background: </strong>Gallstones, a common surgical condition globally, affect around 20% of patients. The development of gallstones is linked to abnormal cholesterol and bilirubin metabolism, reduced gallbladder function, insulin resistance, biliary infections, and genetic factors. In addition to these factors, research has shown that mucins play a role in gallstone formation. This study aims to explore the connection between different types of gallstones and mucin gene polymorphisms.</p><p><strong>Methods: </strong>For this purpose, a total of 121 patients with gallbladder stones PNS and 107 patients with healthy controls PNS were enrolled in this case-control study. One SNPs (rs4072037) of MUC1 gene、 three SNPs (rs2856111、rs41532344、rs41349846) of MUC2 gene、four SNPs (rs712005、rs2246980、rs2258447、rs2259292) of MUC4 gene、seven SNPs (rs28415193、rs56047977、rs2037089、rs2075854、rs3829224、rs2672785、rs2735709) of MUC5 gene、eight SNPs (rs10902268、rs61869016、rs573849895、rs59257210、rs7396383、rs74644072、rs7481521、rs9704308) of MUC6 gene、five SNPs (rs10229731、rs73168398、rs4729655、rs55903219、rs74974199) of MUC17 gene. We amplified SNP sites by polymerase chain reaction (PCR) using specific primer sets followed by DNA sequencing.</p><p><strong>Results: </strong>The frequencies of MUC2 rs2856111 C/T genotype (OR = 3.81, 95%CI: 1.06-13.68) was higher than the control group. MUC17 rs10229731 A/C genotype (OR = 0.33, 95%CI: 0.12-0.95), rs73168398 G/A genotype (OR = 0.26, 95%CI: 0.07-0.98), MUC6 rs10902268 G/A genotype (OR = 0.40, 95%CI: 0.17-0.95) at lower frequencies than controls. The frequencies of MUC2 rs41532344 T allele (OR = 2.55, 95%CI: 1.06-6.13), MUC4 rs712005 G allele (OR = 2.51, 95%CI: 1.20-5.22), MUC5B rs2037089 C allele (OR = 3.54, 95%CI: 1.14-11.01) and MUC5AC rs28415193 G allele (OR = 1.77, 95%CI: 1.02-3.07) were higher than the control group. MUC6 rs10902268 A allele (OR = 0.004, 95%CI: 0.00-0.27), rs61869016 C allele (OR = 0.07, 95%CI: 0.01-0.63) at lower frequencies than controls.</p><p><strong>Conclusions: </strong>Polymorphisms in the mucin gene were linked to the formation of gallbladder stones. The MUC4 rs712005 G allele, MUC5B rs2037089 C allele, MUC2 rs41532344 T allele and MUC5AC rs28415193 G allele were found to predispose individuals to the development of the disease. MUC6 rs10902268 A allele and rs61869016 C allele were identified as protective factors. Meanwhile, MUC2 rs2856111 CT genotype was found to predispose individuals to the development of the disease. MUC17 rs10229731 AC genotype, rs73168398 GA genotype and MUC6 rs10902268 GA genotype were identified as protective factors.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"22"},"PeriodicalIF":2.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying novel heterozygous PI4KA variants in fetal abnormalities.","authors":"Chen Cheng, Fan Yang, Xinlin Chen, Sheng Zhao","doi":"10.1186/s12920-025-02093-9","DOIUrl":"10.1186/s12920-025-02093-9","url":null,"abstract":"<p><strong>Background: </strong>The clinical manifestations of PI4KA-related disorders are characterized by considerable variability, predominantly featuring neurological impairments, gastrointestinal symptoms, and a combined immunodeficiency. The aim of this study was to delineate the novel spectrum of PI4KA variants detected prenatally and to assess their influence on fetal development.</p><p><strong>Methods: </strong>A thorough fetal ultrasound screening was conducted, supplemented by both antenatal and post-abortion magnetic resonance imaging (MRI) studies. Novel PI4KA variants were detected through clinical Whole exon sequencing (WES) and validated by Sanger sequencing. The functional consequences of these variants were evaluated using bioinformatics tools. The effects of the identified variants on splicing were analyzed through minigene splicing assays. Subsequently, both wild-type and mutant PI4KA protein fragments were purified, and their enzymatic activities were quantitatively assessed.</p><p><strong>Results: </strong>Ultrasound imaging, MRI scans revealed a dilated small intestine with an obstruction. Compound heterozygous variants (NM_058004.3: c.2802_2863-40del and c.2819 C > T, p.Ala940Val) were identified in the PI4KA of the affected fetus through clinical trio-WES. Both variants were predicted deleterious. The PI4KA variant c.2802_2863-40del resulted in the production of three distinct mRNA isoforms. The PI4KA variant c.2819 C > T (p.Ala940Val) significantly reduced the enzyme activity.</p><p><strong>Conclusions: </strong>This study extended the mutational spectrum of PI4KA and may provide guidance for genetic counseling. Functional studies confirmed that the identified variant induces alterations in RNA splicing and impairs enzyme activity.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"23"},"PeriodicalIF":2.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and evaluation of patient-centred polygenic risk score reports for glaucoma screening.","authors":"Georgina L Hollitt, Mark M Hassall, Owen M Siggs, Jamie E Craig, Emmanuelle Souzeau","doi":"10.1186/s12920-024-02079-z","DOIUrl":"10.1186/s12920-024-02079-z","url":null,"abstract":"<p><strong>Background: </strong>Polygenic risk scores (PRS), which provide an individual probabilistic estimate of genetic susceptibility to develop a disease, have shown effective risk stratification for glaucoma onset. However, there is limited best practice evidence for reporting PRS and patient-friendly reports for communicating PRS effectively are lacking. Here we developed patient-centred PRS reports for glaucoma screening based on the literature, and evaluated them with participants using a qualitative research approach.</p><p><strong>Methods: </strong>We first reviewed existing PRS reports and literature on probabilistic risk communication. This informed the development of a draft glaucoma screening PRS report for a hypothetical high risk individual from the general population. We designed three versions of the report to illustrate risk using a pictograph, a pie chart and a bell curve. We then conducted semi-structured interviews to assess preference of visual risk communication aids, understanding of risk, content, format and structure of the reports. Participants were invited from an existing study, which aims to evaluate the clinical validity of glaucoma PRS among individuals > 50 years from the general population. Numeracy and literacy levels were assessed.</p><p><strong>Results: </strong>We interviewed 12 individuals. The cohort was highly educated (42% university education), all were European and 50% were female. Numeracy (mean 2.1 ± 0.9, range 0 to 3), graph literacy (mean 2.8 ± 0.8, range 0 to 4) and genetic literacy (mean 24.2 ± 6.2, range - 20 to + 46) showed a range of levels. We analysed the reports under three main themes: visual preferences, understanding risk and reports formatting. The visual component was deemed important to understanding risk, with the pictograph being the preferred visual risk representation, followed by the pie chart and the bell curve. Participants expressed preference for absolute risk in understanding risk, along with the written content explaining the results. The importance of follow-up recommendations and time to glaucoma onset were deemed important. Participants expressed varied opinions in the level of information and the colours used, which informed revisions of the report.</p><p><strong>Conclusions: </strong>Our study revealed preferences for reporting PRS information in the context of glaucoma screening, to support the development of clinical PRS reporting. Further research is needed to assess PRS communication in other groups representative of target populations and with other target audiences (e.g. referring clinicians), and its potential psychosocial impact in the wider community.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"21"},"PeriodicalIF":2.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A dedicated caller for DUX4 rearrangements from whole-genome sequencing data.","authors":"Pascal Grobecker, Stefano Berri, John F Peden, Kai-Jie Chow, Claire Fielding, Ivana Armogida, Helen Northen, David J McBride, Peter J Campbell, Jennifer Becq, Sarra L Ryan, David R Bentley, Christine J Harrison, Anthony V Moorman, Mark T Ross, Martina Mijuskovic","doi":"10.1186/s12920-024-02069-1","DOIUrl":"10.1186/s12920-024-02069-1","url":null,"abstract":"<p><p>Rearrangements involving the DUX4 gene (DUX4-r) define a subtype of paediatric and adult acute lymphoblastic leukaemia (ALL) with a favourable outcome. Currently, there is no 'standard of care' diagnostic method for their confident identification. Here, we present an open-source software tool designed to detect DUX4-r from short-read, whole-genome sequencing (WGS) data. Evaluation on a cohort of 210 paediatric ALL cases showed that our method detects all known, as well as previously unidentified, cases of IGH::DUX4 and rearrangements with other partner genes. These findings demonstrate the possibility of robustly detecting DUX4-r using WGS in the routine clinical setting.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"24"},"PeriodicalIF":2.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of MTHFD1 G1958A (rs2236225) gene polymorphism with the risk of congenital heart disease: a systematic review and meta-analysis.","authors":"Kang Yi, Shao-E He, Tao Guo, Zi-Qiang Wang, Xin Zhang, Jian-Guo Xu, Hao-Yue Zhang, Wei-Guo Liu, Tao You","doi":"10.1186/s12920-024-02052-w","DOIUrl":"10.1186/s12920-024-02052-w","url":null,"abstract":"<p><strong>Background: </strong>We did this study to better clarify the correlations of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1)-G1958A (rs2236225) gene polymorphism with the risk of congenital heart diseases (CHD) and its subgroups.</p><p><strong>Methods: </strong>Relevant articles were searched in PubMed, Web of Science, Cochrane Library, Embase, CNKI, VIP database and Wanfang DATA until October 2023. We will use odds ratios (ORs) and 95% confidence intervals (CIs) to examine the potential associations of MTHFD1- G1958A gene polymorphism with CHD and its subgroups.</p><p><strong>Results: </strong>We included a total of 9 eligible studies, encompassing 1917 children with CHD, 1863 healthy children, 1717 mothers of the children with CHD and 1666 mothers of healthy children. In our study, the meta-analysis of fetal group revealed no significant association between any of the five genetic models for the MTHFD1-G1958A polymorphism and the risk of CHD. Subgroup analysis showed that associations between the MTHFD1-G1958A polymorphism and Tetralogy of Fallot (TOF) risk in the homozygote model (AA vs. GG, OR = 2.82, 95%CI [1.16, 6.86], P = 0.02) and recessive model (AA vs. GG + GA, OR = 3.09, 95%CI [1.36, 7.03], P = 0.007). In addition, the MTHFD1-G1958A polymorphism was associated with the risk of CHD in racial subgroup, increasing the risk of CHD in Caucasians. In maternal analysis, 2 genetic models of MTHFD1-G1958A polymorphism increased the risk of CHD: the heterozygote model (GA vs. GG, OR = 1.22, 95%CI [1.04, 1.42], P = 0.01), and the dominance model (GA + AA vs. GG, OR = 1.17, 95%CI [1.01, 1.34], P = 0.03).</p><p><strong>Conclusions: </strong>The fetal MTHFD1-G1958A (rs2236225) gene polymorphism increase their risk of TOF. The maternal MTHFD1-G1958A polymorphism has a strong correlation with the risk of CHD, and there are racial differences in this correlation. Compared with GG genotype, the GA genotype increases the risk of CHD.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"20"},"PeriodicalIF":2.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of novel cytoskeleton protein involved in spermatogenic cells and sertoli cells of non-obstructive azoospermia based on microarray and bioinformatics analysis.","authors":"Danial Hashemi Karoii, Hossein Azizi, Maryam Darvari, Ali Qorbanee, Dawan Jamal Hawezy","doi":"10.1186/s12920-025-02087-7","DOIUrl":"10.1186/s12920-025-02087-7","url":null,"abstract":"<p><strong>Background: </strong>During mammalian spermatogenesis, the cytoskeleton system plays a significant role in morphological changes. Male infertility such as non-obstructive azoospermia (NOA) might be explained by studies of the cytoskeletal system during spermatogenesis.</p><p><strong>Methods: </strong>The cytoskeleton, scaffold, and actin-binding genes were analyzed by microarray and bioinformatics (771 spermatogenic cellsgenes and 774 Sertoli cell genes). To validate these findings, we cross-referenced our results with data from a single-cell genomics database.</p><p><strong>Results: </strong>In the microarray analyses of three human cases with different NOA spermatogenic cells, the expression of TBL3, MAGEA8, KRTAP3-2, KRT35, VCAN, MYO19, FBLN2, SH3RF1, ACTR3B, STRC, THBS4, and CTNND2 were upregulated, while expression of NTN1, ITGA1, GJB1, CAPZA1, SEPTIN8, and GOLGA6L6 were downregulated. There was an increase in KIRREL3, TTLL9, GJA1, ASB1, and RGPD5 expression in the Sertoli cells of three human cases with NOA, whereas expression of DES, EPB41L2, KCTD13, KLHL8, TRIOBP, ECM2, DVL3, ARMC10, KIF23, SNX4, KLHL12, PACSIN2, ANLN, WDR90, STMN1, CYTSA, and LTBP3 were downregulated. A combined analysis of Gene Ontology (GO) and STRING, were used to predict proteins' molecular interactions and then to recognize master pathways. Functional enrichment analysis showed that the biological process (BP) mitotic cytokinesis, cytoskeleton-dependent cytokinesis, and positive regulation of cell-substrate adhesion were significantly associated with differentially expressed genes (DEGs) in spermatogenic cells. Moleculare function (MF) of DEGs that were up/down regulated, it was found that tubulin bindings, gap junction channels, and tripeptide transmembrane transport were more significant in our analysis. An analysis of GO enrichment findings of Sertoli cells showed BP and MF to be common DEGs. Cell-cell junction assembly, cell-matrix adhesion, and regulation of SNARE complex assembly were significantly correlated with common DEGs for BP. In the study of MF, U3 snoRNA binding, and cadherin binding were significantly associated with common DEGs.</p><p><strong>Conclusion: </strong>Our analysis, leveraging single-cell data, substantiated our findings, demonstrating significant alterations in gene expression patterns.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"19"},"PeriodicalIF":2.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}