Frontiers in Genetics最新文献

{"title":"Mesenchymal stem cells and exosomes in ischemic brain injury: a review.","authors":"Haiyan Xu, Lanlan Yang, Weitie Wang, Chengwei Zhang","doi":"10.3389/fgene.2025.1639756","DOIUrl":"10.3389/fgene.2025.1639756","url":null,"abstract":"<p><p>Stroke poses a serious threat to human health and life, serving as a leading cause of death and disability in adults. The incidence rate of stroke continues to rise annually. Following the onset of ischemic stroke, most patients experience a period of spontaneous recovery. Neural repair after cerebral ischemia is closely associated with neurovascular plasticity, which facilitates the regeneration and repair of nerves and blood vessels in the ischemic injury area. Mesenchymal stem cells (MSCs), adult stem cells isolated from bone marrow or other tissues, can differentiate into various cell types and possess characteristics such as self-renewal, low immunogenicity, and easy of isolation. Exosomes are regarded as the primary mediators of MSC functions. These specialized extracellular vesicles play critical roles in intercellular communication, targeted transport, and regulation of recipient cell functions through their surface molecules and cargo (e.g., proteins, RNA, and other bioactive factors). Studies demonstrate that MSCs and their exosomes participate in both neuronal and vascular endothelial cell damage and repair after stroke. They exert distinct effects at different stages of cerebral ischemia injury, promoting angiogenesis, neurogenesis, and reducing inflammation. While preclinical studies show promising therapeutic potential, clinical translation faces challenges such as standardization of exosome isolation, optimal dosing, delivery methods, and long-term safety evaluation. Future research should focus on overcoming these barriers to facilitate their application in stroke therapy. This review summarizes current research on the therapeutic potential of MSCs and their exosomes in ischemic brain injury.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1639756"},"PeriodicalIF":2.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Engineering novel features for diabetes complication prediction using synthetic electronic health records.","authors":"Daniel Voskergian, Burcu Bakir-Gungor, Malik Yousef","doi":"10.3389/fgene.2025.1687832","DOIUrl":"10.3389/fgene.2025.1687832","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fgene.2025.1451290.].</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1687832"},"PeriodicalIF":2.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Emerging relevance of molecular profiling in global cancer research and management.","authors":"Premila Leiphrakpam, Srijan Shukla, Chandrakanth Are","doi":"10.3389/fgene.2025.1679501","DOIUrl":"10.3389/fgene.2025.1679501","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1679501"},"PeriodicalIF":2.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and validation of a histone modification-related gene signature to predict the prognosis of multiple myeloma.","authors":"Juan Lyu, Shanmei Lyu, Ying Qian, Yi Feng, Zhuan Zheng, Lihong Zhang","doi":"10.3389/fgene.2025.1613631","DOIUrl":"10.3389/fgene.2025.1613631","url":null,"abstract":"<p><strong>Background: </strong>Multiple myeloma (MM) is an incurable plasma cell malignancy with high heterogeneity. Current staging systems, including the International Staging System (ISS) and Revised ISS (R-ISS), have limited prognostic accuracy. Given the role of histone modifications in MM progression, we developed a histone modification-related (HMR) prognostic model to improve MM risk stratification.</p><p><strong>Methods: </strong>Gene expression and mutation data were downloaded from the Gene Expression Omnibus database and the Cancer Genome Atlas. Prognostic HMR-related genes were identified through a combination of univariate Cox regression, least absolute shrinkage and selection operator Cox regression, and random survival forest analysis. The genes identified were then used to construct the HMR risk score model using multivariate Cox regression. The model was validated using Kaplan-Meier survival, time-dependent receiver operating characteristic curves analysis. A nomogram combining the HMR score with clinical features was developed. Functional enrichment, immune infiltration, somatic mutation, and drug sensitivity analysis were conducted to explore the biological relevance of the model.</p><p><strong>Results: </strong>Seven HMR genes with prognostic significance were identified. The HMR risk score stratified patients into high-risk and low-risk groups, with significant survival differences. The model demonstrated favorable predictive performance, and was shown to be an independent prognostic factor. The nomogram showed good calibration and discriminative ability, offering a practical tool for individual patient risk assessment. Functional analysis revealed that the HMR risk score is associated with dysregulated cell cycle progression, proliferation, and immunosuppression in MM, which may contribute to disease progression and drug resistance. Moreover, drug sensitivity analysis indicated potential associations between the HMR score and response to specific therapeutic agents, highlighting its potential role in guiding personalized treatment.</p><p><strong>Conclusion: </strong>We developed an HMR gene signature that has potential for prognostic prediction and may help guide personalized treatment strategies in MM.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1613631"},"PeriodicalIF":2.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel estrogen-related gene variants identified by whole-exome sequencing in pregnancy-associated intrahepatic cholestasis.","authors":"Hua Lai, Siming Xin, Jinliang Zhang, Yang Hu, Wenjuan Fan, Hong Wan, Bowen Chen, Yang Zou, Xiaoming Zeng, Xianxian Liu","doi":"10.3389/fgene.2025.1626890","DOIUrl":"10.3389/fgene.2025.1626890","url":null,"abstract":"<p><p>Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse fetal outcomes, including fetal morbidity and mortality. It is a complex liver disorder influenced by genetic interactions, estrogen levels, and environmental factors. Although elevated estrogen levels are known to contribute to ICP pathogenesis, the role of genetic variants in estrogen-related genes remains poorly characterized. Accordingly, we conducted whole-exome sequencing (WES) in 249 patients with ICP, focusing on eight key estrogen-related genes (<i>ESR1/2, CYP17A1/19A1, CYP1A2/1B1/3A4</i>, and <i>COMT</i>). Variants were validated by Sanger sequencing and functionally characterized using comprehensive bioinformatics analyses (PolyPhen-2, SIFT, and MutationTaster) combined with molecular modeling. Our whole-exome sequencing analysis of 249 patients with ICP identified 235 variants across eight estrogen-related genes, with three novel <i>CYP17A1</i> missense mutations (p.Pro28Thr, p.Phe93Leu, and p.Arg347Leu) demonstrating particularly significant findings. These variants exhibited the following characteristics: (1) complete absence in 1,237 controls and all public genomic databases (1000 Genomes, ExAC, and dbSNP); (2) evolutionary conservation of the affected residues, with unanimous pathogenic predictions from all algorithms (PolyPhen-2: damaging; SIFT: deleterious; MutationTaster: disease-causing); (3) molecular modeling demonstrating structural perturbations in critical functional domains, including steroid-binding and redox partner interaction sites. Furthermore, analysis of placental tissue revealed significantly reduced <i>CYP17A1</i> expression in ICP cases <i>versus</i> controls (<i>P</i> < 0.05), suggesting functional impairment of estrogen metabolic pathways. We identified three novel pathogenic <i>CYP17A1</i> variants associated with ICP through whole-exome sequencing, elucidated their structural and functional effects on estrogen metabolism, and demonstrated significantly reduced placental <i>CYP17A1</i> expression, thereby providing crucial insights into the genetic basis of ICP pathogenesis.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1626890"},"PeriodicalIF":2.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compound heterozygous missense and intronic variants in <i>B9D1</i> contribute to a recurrent Meckel syndrome pedigree.","authors":"Huining Jing, Bocheng Xu, Hao Wang, Shanling Liu, He Wang, Jingqun Mai, Wencong Yao, Zhu Zhang","doi":"10.3389/fgene.2025.1663455","DOIUrl":"10.3389/fgene.2025.1663455","url":null,"abstract":"<p><strong>Background: </strong>Meckel syndrome (MKS) is an embryonically lethal ciliopathy with severe clinical manifestations, including defects of the central nervous system, bilateral renal cystic dysplasia, and postaxial polydactyly. B9 domain-containing 1 (B9D1, NP_056496.1) is a member of a small family of proteins associated with basal bodies and primary cilia in mammalian cells. <i>B9D1</i> variants are associated with MKS and Joubert syndrome. However, to date, only a few cases have been reported.</p><p><strong>Methods: </strong>In this study, we investigated a prenatally diagnosed recurrent MKS pedigree. Two fetuses of different sexes were conceived by nonconsanguineous parents. Systematic color Doppler ultrasound revealed same malformations in both fetuses during the second trimester, which included meningoencephalocele, Dandy-Walker malformation, and postaxial polydactyly. Trio whole exome sequencing (WES) and WES reanalysis were performed. The presence and effects of these variants were further validated using Sanger sequencing, RT-PCR, and minigene splicing assay at the DNA and RNA levels.</p><p><strong>Results: </strong>Two compound heterozygous variants, c.341G>T (p.R114L) and c.405-308_405-304del, were identified in both probands, each inherited from one unaffected parent. Both variants led to abnormal splicing. Specifically, the missense mutation c.341G>T caused the skipping of exon 4, whereas the novel deep-intronic variant c.405-308_405-304del created a new and strong acceptor site at c.405-294_405-293. Pathogenicity analysis indicated that both variants were pathogenic.</p><p><strong>Conclusion: </strong>This report presents a rare pedigree of recurrent MKS, in which two novel mutations in <i>B9D1</i> are identified. Our findings expand the mutation spectrum of <i>B9D1</i> and provide an accurate molecular diagnosis for genetic counseling.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1663455"},"PeriodicalIF":2.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and penetrance of pathogenic and likely pathogenic <i>LDLR</i> and <i>APOB</i> gene variants linked to familial hypercholesterolemia and increased risk of ischemic heart disease.","authors":"I K Dzhumaniiazova, A N Meshkov, V V Daniel, M V Ezhov, E A Zelenova, U V Chubykina, D A Kashtanova, M V Ivanov, L R Matkava, O I Blinova, N A Kumar, A Y Fedorov, H U Ibragimova, T A Lavrikova, Y O Aksenova, T M Gurciev, N V Gomyranova, Y S Vorobeva, Z B Hasanova, V S Yudin, V V Makarov, A A Keskinov, S A Kraevoy, S A Boytsov, S M Yudin, V I Skvortsova","doi":"10.3389/fgene.2025.1589014","DOIUrl":"10.3389/fgene.2025.1589014","url":null,"abstract":"<p><strong>Background: </strong>Familial hypercholesterolemia (FH) is a prevalent hereditary disorder, with its monogenic form linked to an elevated risk of early-onset ischemic heart disease. Evaluating the prevalence and penetrance of pathogenic and likely pathogenic variants associated with this disorder would provide valuable information supporting routine FH screening of the general population. Such informed screening would facilitate early identification of at-risk individuals, enabling timely intervention and management.</p><p><strong>Methods: </strong>We analyzed genetic data from 4,856 individuals with various cardiovascular conditions for pathogenic and likely pathogenic variants in the PCSK9, APOB, and LDLR genes. The evaluation included comprehensive clinical assessments, instrumental examinations, and laboratory tests. All genetic data were obtained through the whole-genome sequencing of blood leukocytes.</p><p><strong>Results: </strong>A total of 1.77% of participants carried pathogenic or likely pathogenic variants in the LDLR or APOB genes, and none in the PCSK9 gene. After adjusting for sex and age, the risk of ischemic heart disease was 1.3 times higher in carriers of pathogenic or likely pathogenic variants [95% CI 1.18-1.46; <i>p</i> = 5*10-7]. Additionally, the carriers presented with significantly higher levels of total cholesterol and LDL-C (<i>p</i> = 0.00032 and <i>p</i> = 0.0123, respectively).</p><p><strong>Conclusion: </strong>FH remains significantly underdiagnosed. Only 10.5% of carriers of pathogenic or likely pathogenic variants in the LDLR and APOB genes had a prior diagnosis of FH. Our findings suggest low diagnostic rates for this disorder in Eastern European populations and highlight the need for routine genetic screening of younger individuals. However, further research is needed to assess the clinical applicability and cost-effectiveness of such screening programs.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1589014"},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A retrospective study for the diagnostic value of chromosomal microarray analysis in fetuses with high-risk prenatal indications.","authors":"Hui Xiao, Junfang Xiao, Huan Zhang, Shuhui Huang, Qing Lu, Huizhen Yuan, Yongyi Zou, Bicheng Yang, Yanqiu Liu","doi":"10.3389/fgene.2025.1649253","DOIUrl":"10.3389/fgene.2025.1649253","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to determine the diagnostic value of prenatal chromosomal microarray analysis (CMA) for fetuses at high risk for various conditions on chromosomal abnormalities.</p><p><strong>Methods: </strong>In the study, 8,560 clinical samples were collected from pregnant women between February 2018 and June 2022, including 75 villus, 7,642 amniotic fluid, and 843 umbilical cord blood samples. All samples were screening for chromosomal abnormalities using both CMA and karyotyping. This retrospective analysis included 8,560 pregnancies with high-risk indications for invasive prenatal diagnosis, mainly including ultrasound anomalies, high risk for maternal serum screening (MMS), high risk for non-invasive prenatal tests (NIPTs), family history of genetic disorders or birth defects, and advanced maternal age (AMA). All samples were evaluated using invasive CMA. The rate of clinically significant genomic imbalances between the different groups was compared.</p><p><strong>Results: </strong>The success rate of CMA was 99.95% (8,556/8,560). A total of 1,037 samples (12.11%, 1,037/8,560) were presented with chromosomal abnormalities using CMA, whereas 803 samples (9.38%, 803/8,560) were shown with chromosomal abnormalities using karyotyping. The overall prenatal diagnostic yield was 1,040 (12.14%) of 8,560 pregnancies. Clinically significant genomic aberrations were identified in 153 (6.21%) of 2,463 patients with non-structural ultrasound anomalies, 79 (6.38%) of 1,238 with structural ultrasound anomalies, 37 (4.26%) of 868 at high risk from MSS, 395 (42.29%) of 934 at high risk from NIPTs, 16 (2.94%) of 544 with a family history, 7 (1.89%) of 369 with AMA, 1 (1.56%) of 64 with a history of adverse exposure, 10 (4.46%) of 224 with parental chromosome anomaly, and 9 (2.99%) of 301 with other indications.</p><p><strong>Conclusion: </strong>CMA has a greater diagnostic value for screening chromosomal abnormalities, especially in pregnant women with normal karyotypes. The diagnostic yields of CMA for pregnancies with different indications greatly varied. CMA could serve as a first-tier test for structural anomalies, especially multiple anomalies, hydrops fetalis, cystic hygroma, and thickened nuchal translucency or nuchal fold.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1649253"},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of sex-dependent serum metabolomic patterns across the lifespan of rhesus macaques.","authors":"Ludwig A P Metzler, Robinson W Goy, Jeanette M Metzger, Marina E Emborg, Amita Kapoor","doi":"10.3389/fgene.2025.1655325","DOIUrl":"10.3389/fgene.2025.1655325","url":null,"abstract":"<p><strong>Introduction: </strong>Aging is accompanied by systemic metabolic changes that contribute to disease susceptibility and functional decline. Sex differences in aging have been reported in humans, yet their mechanistic basis remains poorly understood. Due to their physiological similarity to humans, rhesus macaques are a powerful translational model to investigate sex-specific metabolomic aging under controlled conditions.</p><p><strong>Methods: </strong>Targeted serum metabolomics were conducted in 58 rhesus (35 females, 23 males), ranging from 1.66 to 25.71 years of age, quantifying 513 metabolites spanning lipids, amino acids, and related compounds. Multivariate, univariate, and generalized additive model (GAM) analyses were performed to evaluate age-associated trajectories and test for sex differences.</p><p><strong>Results: </strong>Age-related changes in both sexes were identified in metabolites related to hormones (e.g., DHEAS), amino acid biosynthesis and catabolism (e.g., beta-alanine, sarcosine, t4-OH-pro), and energy metabolism (e.g., hexose). Sex affected age-related metabolic trajectories in lipids, amino acids and related compounds, and gut microbial species. Females demonstrated a profound increase in serum triglycerides (TGs), amino acids, and other small molecules, while males exhibited a heterogenous profile with changes in lipids, but no TGs were affected. Males also exhibited altered levels of amino acids and related metabolites, hormones, gut microbial metabolites, and energy-associated metabolites.</p><p><strong>Conclusion: </strong>These results highlight pronounced sex differences in metabolomic aging trajectories in rhesus macaques, particularly in lipid and amino acid metabolism. These findings underscore the importance of incorporating sex as a biological variable in aging studies and support the utility of rhesus macaques for identifying conserved, sex-specific biomarkers of biological aging.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1655325"},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of complex chromosomal structural variants through optical genome mapping integrated with karyotyping.","authors":"Xiaoxi Zhu, Huiling Zheng, Xue Wan, Hang Duan, Ying Qi, Weijia Tang, Fan Yang, Limei Yu","doi":"10.3389/fgene.2025.1605461","DOIUrl":"10.3389/fgene.2025.1605461","url":null,"abstract":"<p><strong>Background and objective: </strong>Parental chromosomal structural variations (SVs) represent a primary genetic factor contributing to recurrent spontaneous abortion (RSA). Individuals carrying SVs with complex chromosomal rearrangements (CCRs) typically exhibit a normal phenotype but are at an increased risk of miscarriage. Current standard clinical detection methods are insufficient for the identification and interpretation of all SV types, particularly complex and occult SVs, thereby presenting a significant challenge for clinical genetic counseling. Leveraging the high-resolution capabilities of optical genome mapping (OGM) technology, this study aims to rapidly and accurately identify complex SVs in RSA couples. Furthermore, it seeks to conduct an in-depth analysis of the genetic information within the breakpoint regions, thereby providing a more comprehensive scientific foundation for genetic counseling of RSA couples at both the cellular and genetic levels.</p><p><strong>Material and methods: </strong>This study involved the selection of nine subjects from two families who underwent genetic counseling at our hospital. Family 1 comprised a couple with the wife as a SVs carrier, and both her parents and brother were simultaneously analyzed for chromosomal karyotype. Family 2 included a couple with the husband as the SVs carrier, with his parents also undergoing chromosomal karyotype analysis. For SVs carriers whose karyotype analysis did not elucidate the recombination pattern, optical genome mapping (OGM) technology was utilized for further investigation, followed by Sanger sequencing to validate the OGM findings.</p><p><strong>Results: </strong>In Family 1, only the wife was identified as an SVs carrier. Initial chromosomal karyotype analysis suggested a karyotype of 46,XX,t (5; 6;8; 13; 15) (?). However, OGM analysis ultimately confirmed the karyotype as 46,XY,der (5)t (5; 13) (q35.2; q21.32), der (6)t (6; 8) (q25.3; q13.1)ins (6; 13) (q25.3; q21.32q21.33),der (8)t (6; 8) (q26; q13.1)ins (8; 13) (q13.1; q21.33q22.1),der (13)t (13; 15) (q21.32; q26.1)ins (13; 6) (q21.32; q25.3q26), der (15)t (5; 15) (q35.2; q26.1). Furthermore, OGM identified a novel translocation variant of the <i>KIF7</i> gene that is associated with recurrent miscarriage. In Family 2, both the husband and his maternal parent were identified as SVs carriers. Nuclear type analysis revealed a karyotype of 46,XY,?t (1; 6) (q42; p21) (husband) and 46,XX,?t (1; 2) (p31.1; q24.1),?t (1; 6) (q42; p21) (mother). Through OGM detection and analysis, the final karyotype was determined to be 46,XY,ins (1; 6) (q42.2; p22.3p11.3) (husband) and 46,XX,der (1)t (1; 2) (p31.1; q24.1)ins (1; 6) (q42.2; p22.3p11.3), der (2) t (1; 2), der (6)ins (1; 6) (mother).</p><p><strong>Conclusion: </strong>OGM technology facilitates the rapid and precise identification of complex chromosomal structural variations, effectively overcoming the limitations associated with traditional karyotype ","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1605461"},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}