Genetic testing and molecular biomarkers最新文献

{"title":"Reclaiming Genomics: Privacy, Direct-to-Consumer Genetic Testing, and the Revolution We Still Need.","authors":"Sharon F Terry","doi":"10.1089/gtmb.2025.0135","DOIUrl":"10.1089/gtmb.2025.0135","url":null,"abstract":"","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"129-130"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spectrum and Frequencies of Genes for Inherited Hearing Loss in Southwestern Chinese Families.","authors":"Yuanyuan Xiao, Li Wang, Cong Zhou, Hanbing Xie, Shuang Huang, Jing Wang, Shanling Liu","doi":"10.1089/gtmb.2024.0281","DOIUrl":"10.1089/gtmb.2024.0281","url":null,"abstract":"<p><p><b><i>Background:</i></b> Inherited hearing loss is an extremely heterogeneous and often ethnicity-specific disorder, with more than 150 genes identified to date. Thus, clinical diagnosis is challenging, particularly because of the thousands of different severe causal mutations between populations. <b><i>Materials and methods:</i></b> In this study, we aimed to identify the mutational spectra associated with hearing loss in 89 Southwestern Chinese families. We used a hearing loss-targeted panel to sequence 163 genes known to cause or be candidate genes for hearing loss. The targeted panel was implemented to 89 families with syndromic or nonsyndromic hearing loss. <b><i>Results:</i></b> Of the total 89 patients, 55 patients carried 101 pathogenic/likely pathogenic alleles, providing a genetic diagnosis in 61.80%. <i>GJB2</i> variants were predominant, with a frequency of 43.6% among all variants, followed by variants of <i>SLC26A4</i> (31.7%), <i>MYO15A</i> (5.9%), and <i>MT-RNR1</i> (5%). These 4 genes accounted for 80.56% (87/108) of all identified alleles. Furthermore, 3 of the 89 patients carried 7 alleles of unknown significance. In total, 45 variants were identified, including 35 variants reported in the Human Gene Mutation Database Professional and 10 novel variants that had not been previously reported. <b><i>Conclusion:</i></b> Our findings provide a survey of the mutation spectrum in patients with hearing loss from Southwestern Chinese families. This highlights the fact that genomic sequencing with a selected gene panel specific to hearing loss is effective for its genetic diagnosis.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"131-137"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering a Diagnosis Through Reanalysis of <i>UBA2</i> Variants in a Patient with Syndactyly, Polydactyly, and Aplasia Cutis Congenita: A Short Report and a Review of the Literature.","authors":"Khurram Liaqat, Kimberly Felipe, Kayla Treat, Molly McPheron, David D Weaver, Francesco Vetrini, Erin Conboy","doi":"10.1089/gtmb.2025.0042","DOIUrl":"https://doi.org/10.1089/gtmb.2025.0042","url":null,"abstract":"<p><p><b><i>Background:</i></b> Aplasia cutis congenita and ectrodactyly skeletal syndrome (ACCES) is caused by heterozygous variants in the <i>UBA2</i> gene, with phenotypic heterogeneity encompassing a range of diverse skeletal, dermatological, and neurological features. <b><i>Aims:</i></b> The goal of our research was to suggest that pathogenic frameshift variant c.52_58dupGGCCGGG p.(Val20Gfs*31) could lead to the development of ACCES and also to review the literature to document phenotypic variability among individuals with <i>UBA2</i> variants, providing further insights into this ultrarare syndrome. <b><i>Methods and Result:</i></b> We report a case of a 7-year-old male presenting with cutis aplasia congenita, syndactyly, preaxial polydactyly, and severe hypospadias. Exome sequencing (ES) identified a heterozygous frameshift variant c.52_58dupGGCCGGG p.(Val20Gfs*31) in the <i>UBA2</i> gene. This variant is absent in gnomAD and is predicted to cause a premature stop codon with consequent protein truncation and/or nonsense-mediated decay. Initially classified as a variant of uncertain significance, this frameshift variant was reclassified as pathogenic following a comprehensive reassessment post-enrollment of the patient in the Undiagnosed Rare Disease Clinic of Indiana University School of Medicine. <b><i>Conclusion:</i></b> This study illustrates the critical role of ongoing genomic data reevaluation, particularly in unsolved cases, where variant reclassification has the potential to impact diagnostic precision, targeted treatment planning, and family counseling. The clinical variability observed among reported cases, spanning mild to severe presentations, underscores the complexity of <i>UBA2</i>-related disorders. This variability suggests an interplay of genetic modifiers, epigenetic influences, and environmental factors, highlighting the need for further research into the mechanisms driving this heterogeneity.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":"29 4","pages":"120-128"},"PeriodicalIF":1.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Expression Profiles of mRNAs, LncRNAs, and CircRNAs in the Colon Specimens of Patients with Slow Transit Constipation.","authors":"Mingming Sun, Yahui Wang, Huiju Yang, Xiaopeng Wang, Lianlin Su, Shuai Yan","doi":"10.1089/gtmb.2024.0472","DOIUrl":"https://doi.org/10.1089/gtmb.2024.0472","url":null,"abstract":"<p><p>Slow transit constipation (STC) is a complication of depression that can negatively impact patient prognosis and quality of life. Nonetheless, the pathogenesis of STC is unclear. In this work, colon tissues from STC and non-STC patients were utilized to determine transcriptome expression patterns (messenger ribonucleic acids [mRNAs], Long noncoding RNAs [lncRNAs], and Circular RNAs [circRNAs]) via high-throughput sequencing. We found that 4430 mRNAs, 984 lncRNAs, and 2152 circRNAs exhibited substantial variations in expression patterns in the colon tissues of STC and non-STC patients. Next, we constructed a protein-protein interaction network and identified three significant elements, namely, POLR2B, SRSF1, and SUMO1, which attracted our interest. Utilizing the data of 6 upregulated circRNAs and 10 downregulated circRNAs, we created a competing endogenous RNA network. Subsequently, we found that hsa_circ_0000994 and hsa_circ_0008699 were significantly enriched in the upregulated and downregulated networks, respectively. The coexpression network analysis suggested that circRNAs and lncRNAs might exert control over mRNAs by influencing the neural functions of STC. According to the results of the integrated circRNA-miRNA-mRNA network, circRNA-regulated mRNAs were linked to both the transforming growth factor-β (TGF-β) and Notch signaling pathways. Our findings could provide new perspectives for identifying potential prognostic markers in STC. Targeting SUMO1 may present a promising approach to address colonic motility disorders in STC therapy.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":"29 4","pages":"102-119"},"PeriodicalIF":1.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apolipoprotein E and Its Possible Role in the Pathogenesis of Gestational Diabetes Mellitus: Fact or Fiction?","authors":"Kallirhoe Kalinderi, Michail Kalinderis, Vasileios Papaliagkas, Anthoula Chatzikyriakidou, Liana Fidani","doi":"10.1089/gtmb.2024.0500","DOIUrl":"https://doi.org/10.1089/gtmb.2024.0500","url":null,"abstract":"","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":"29 4","pages":"99-101"},"PeriodicalIF":1.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VEXAS Syndrome: A Perspective Focus on Genetics and Hematological Manifestations.","authors":"Evdoxia Sapountzi, Genevieve Crane, Jane Gibson, Hatem Kaseb","doi":"10.1089/gtmb.2024.0426","DOIUrl":"10.1089/gtmb.2024.0426","url":null,"abstract":"","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"49-53"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of the Prognostic Value of m5C Methylation Protein NOP2 and NSUN6 in Colon Cancer.","authors":"Bin Jiang, Jie Li, Jianguo Wang","doi":"10.1089/gtmb.2024.0416","DOIUrl":"10.1089/gtmb.2024.0416","url":null,"abstract":"<p><p><i><b>Background:</b></i> Colorectal cancer is a prevalent malignancy with high incidence and poor prognosis. This study explores the clinical significance of 5-methylcytosine RNA modification factors, specifically the NOP2/Sun RNA Methyltransferase (NSUN) family, in colorectal cancer. <i><b>Methods:</b></i> Utilizing data from The Cancer Genome Atlas database, we analyzed the expression levels of NSUN family members in tumor tissues, their prognostic relevance, and their relationship with immune cell infiltration. To further investigate, paraffin-embedded cancer tissue microarrays were used to assess the expression of NOP2 Nucleolar Protein (NOP2) and NSUN6 in colorectal cancer tissues and adjacent normal tissues. The correlation between the expression of these genes and patient prognosis was also examined. <i><b>Results:</b></i> Bioinformatic analysis revealed that NOP2 is highly expressed in tumors, whereas NOP2/Sun RNA Methyltransferase 6 (NSUN6) is linked to poor prognosis. Immune infiltration analysis demonstrated that NOP2 expression is significantly correlated with varying levels of immune cell infiltration, including a positive association with myeloid-derived suppressor cells (MDSCs), M1 macrophages, and natural killer cells and a negative correlation with regulatory T cells and M2 macrophages. NSUN6 expression showed a significant positive correlation with MDSC infiltration. Clinical sample analysis indicated that NOP2 expression is strongly associated with tumor grade and nerve invasion, whereas NSUN6 is significantly related to nerve invasion. Survival analyses revealed that high levels of NOP2 and NSUN6 are linked to shorter overall survival. Notably, NSUN6 expression, vascular invasion, and T stage emerged as key predictors of colorectal cancer patient survival. <i><b>Conclusions:</b></i> These findings suggest that NOP2 and NSUN6 may serve as valuable molecular markers for predicting poor prognosis in colorectal cancer, with potential applications in clinical decision-making.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"74-84"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast Growth Factor 11 Promotes Immune Escape of Cervical Cancer Cells by Promoting Infiltration of CD4⁺ T Cells, Particularly Regulatory T Cells.","authors":"Xinyi Nie, Ziyan Zhu, Yonglian Liu, Xuran Zhang, Jiangping Chen, Fan Zhang, Bowei Guo","doi":"10.1089/gtmb.2024.0478","DOIUrl":"10.1089/gtmb.2024.0478","url":null,"abstract":"<p><p><b><i>Background:</i></b> Cervical cancer (CC) is one of the leading gynecological malignancies. Immunotherapy has shown limited efficacy, particularly for advanced, recurrent CC. Consequently, dependable prognostic biomarkers and treatment targets are needed. <b><i>Methods and Results:</i></b> In this study, we aimed to determine the association of fibroblast growth factor 11 (<i>FGF11</i>) with prognosis. <i>FGF11</i> expression was assessed in both tissues and cells through immunohistochemical and immunocytochemical staining. Immune cell infiltration was predicted using Tumor Immune Estimation Resource (TIMER) and TIMER2.0. <i>FGF11</i> was significantly correlated with prognosis. <i>FGF11</i> expression was significantly elevated in CC tissues. Moreover, <i>FGF11</i> expression was significantly higher in SiHa and HeLa cancer cells than in normal H8 cells, particularly SiHa cells. Enrichment analyses suggested that <i>FGF11</i> may be involved in arachidonic acid and linoleic acid metabolism, indicating roles in epithelial adhesion and cell differentiation. <i>FGF11</i> correlated positively with CD4⁺ T, regulatory T, and dendritic cells but negatively with CD8⁺ T cells. <i>FGF11</i> also correlated positively with Cluster of Differentiation 4 (<i>CD4), CD25,</i> Forkhead box P3 <i>(FOXP3),</i> and transforming growth factor β but negatively with human leukocyte antigens. <b><i>Conclusions:</i></b> <i>FGF11</i> may enhance the immune escape abilities of CC cells by promoting CD4⁺ T cell infiltration (particularly regulatory T cells) into the tumor microenvironment, leading to poor prognosis. These findings provide a reference for the exploration of <i>FGF11</i> as a prognostic biomarker and treatment target in CC.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":"29 3","pages":"85-98"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preimplantation Genetic Testing in a Family with Neurofibromatosis Type 1.","authors":"Longmei Wang, Xuemei He, Xianjing Huang, Pingping Qiu, Hong Ji, Lu Ding, Yingying Shi, Ping Li, Libin Mei","doi":"10.1089/gtmb.2025.0031","DOIUrl":"10.1089/gtmb.2025.0031","url":null,"abstract":"<p><p><b><i>Background:</i></b> Neurofibromatosis is an autosomal dominant genetic disease caused by the abnormal development of neural crests due to genetic defects and is difficult to treat. Patients have a characteristic phenotype with neurofibromas as the main features in different forms, which are accompanied by multisystem involvement. The clinical symptoms of this disease vary greatly, making the treatment more difficult. <b><i>Methods:</i></b> Preimplantation genetic testing (PGT) is a useful technique to prevent chromosomal aneuploidies and other genetic disorders in origin. PGT for monogenic diseases (PGT-M) is now widely used as an effective strategy to screen embryos for monogenic or chromosomal diseases before implantation. In this study, PGT-M was performed in a family history of hereditary with neurofibromatosis type 1 (NF1) to prevent the offspring from inheriting disease-causing gene variant from their parents. Trio-based whole-exome sequencing was used to identify potential pathogenic variants associated with NF1. Blastocyst biopsy was performed on embryos obtained by intracytoplasmic sperm injection. Single-cell amplification of biopsied cells was performed for targeted next-generation sequencing. Single nucleotide polymorphism markers on both sides of <i>NF1</i> were selected to identify disease-carrying haplotypes in each embryo. <b><i>Results:</i></b> A novel heterozygotic frameshift pathogenic variant, c.2033_2034delinsA(p.P678Qfs*10), was identified in the <i>NF1</i> gene in the proband. A total of five blastocysts were biopsied, and the PGT results showed that only one blastocyst was unaffected and was euploid, and the remaining four blastocysts were all carrying paternal pathogenic variants. The only one normal blastocyst was transferred in a frozen-thawed embryo transfer cycle, and a live singleton pregnancy was successfully achieved. At 18 weeks, the amniocentesis test revealed normal karyotype, and the variant carried by the proband was not detected. At 40 weeks, the proband's wife successfully delivered a healthy baby naturally. <b><i>Conclusion:</i></b> PGT is an effective method to detect chromosome copy number variation and gene variant sites in embryos, and it provides suggestions for possible innovations to block the transmission of single-gene genetic diseases to offspring, thereby preventing the occurrence of birth defects.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"54-62"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of <i>PNPLA3</i> rs738409 C > G and rs2896019 T > G Polymorphisms with Nonalcoholic Fatty Liver Disease in a Turkish Population from Adıyaman Province.","authors":"Süleyman Bayram, Yakup Ülger","doi":"10.1089/gtmb.2024.0481","DOIUrl":"10.1089/gtmb.2024.0481","url":null,"abstract":"<p><p><b><i>Objectives:</i></b> The purpose of this study was to investigate the effect of patatin-like phospholipase domain-containing protein 3 (<i>PNPLA3</i>) rs738409 C > G and rs2896019 T > G polymorphisms on genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) in a Turkish population from Adıyaman province, located in the Southeast Anatolia Region of Turkey. <b><i>Materials and Methods:</i></b> This hospital-based molecular epidemiological case-control study analyzed the <i>PNPLA3</i> rs738409 C > G and rs2896019 T > G polymorphisms in 335 NAFLD cases and 410 healthy controls. Genotype frequencies were determined using real-time polymerase chain reaction with the TaqMan assay. The association with NAFLD susceptibility was evaluated by calculating odds ratios (ORs) and 95% confidence intervals (CIs) using an unconditional logistic regression model. <b><i>Results:</i></b> We found that the <i>PNPLA3</i> rs738409 C > G (CC vs. GG: OR = 1.90, 95% CI = 1.05-3.44) and rs2896019 T > G (TT vs. GG: OR = 3.24, 95% CI = 1.44-7.27) polymorphisms were linked to an increased risk of NAFLD in almost all genetic models (<i>p</i> < 0.05). In addition, the <i>PNPLA3</i> Grs738409/Grs2896019 haplotype was associated with NAFLD development (<i>p</i> < 0.05). Significant differences in alanine aminotransferase and aspartate aminotransferase enzyme levels were observed across the genotypes of these polymorphisms (<i>p</i> < 0.05). <b><i>Conclusion:</i></b> This is the first study on <i>PNPLA3</i> single nucleotide polymorphisms (SNPs) and NAFLD in the Turkish population of Adıyaman Province, Southeast Anatolia. Our findings suggest that the <i>PNPLA3</i> rs738409 C > G and rs2896019 T > G polymorphisms, along with their haplotypes, may influence NAFLD susceptibility. Further independent studies with larger sample sizes and diverse populations are needed to confirm these results.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":"29 3","pages":"63-73"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}