Molecular Genetics and Genomics最新文献

{"title":"Whole genome sequencing and evolutionary significance of a novel mosquitocidal bacterium, Bacillus thuringiensis serovar israelensis VCRC-B650 reported from Union Territory of Puducherry, India highly useful for mosquito control.","authors":"Kakhuangailiu Gangmei, Mathivanan Ashokkumar, Bhavna Gupta, Abhisubesh Vijayakumar, Sahadiya Mandodan, Aneha Kunnikuruvan, Manikandan Sivaprakasam, Hemaladkshmi Padmanaban, Bhagyashree Bora, Jibi Lukose, Geetha Irudayaraj, Poopathi Subbiah","doi":"10.1007/s00438-025-02247-5","DOIUrl":"https://doi.org/10.1007/s00438-025-02247-5","url":null,"abstract":"<p><p>Mosquito-borne diseases pose a significant global health challenge, highlighting the need for innovative biocontrol agents. In this study, a novel mosquitocidal bacterium was isolated from clay soil and subjected to Whole Genome Sequencing (WGS) and bioinformatics analysis to understand its genetic composition and potential applications. WGS revealed that the bacterium a circular genome of size 6,622,317 bp comprising 6930 genes, 115 tRNA and 17 rRNA. The (G + C)s content was found to be 34.83% at the contig level and 34.83% at the scaffold level. Bioinformatics tools, including KmerFinder, Bacterial and Viral Bioinformatics Resource Center and JSpecies, identified the strain as Bacillus thuringiensis serovar israelensis (Bti VCRC-B650). Additionally, eight plasmids were identified in its genome. Notably, the genome analysis confirmed the presence of Cry4Ba, Cry10Aa, Cry15Aa, Cry4Aa, Cry11Aa, Cyt1Aa, Cyt2Ba, Cry2Aa, and Cyt2Ba1 toxins which were considered to be the principal factor of evolutionary significance for mosquitocidal activity. Further analysis identified four different types of Clustered Regularly Interspaced Short Palindromic Repeats sequences, 16 Biosynthetic Gene Clusters, and 312 antibiotic resistance genes. Comparative genomic analysis revealed a total of 556 core genes in Bti VCRC-B650 strain. This study highlights the potential of WGS in characterizing microbial strains with biocontrol properties. The findings suggest that the newly identified Bti VCRC-B650 strain could serve as a promising biological control agent against mosquito larvae and may also have applications in antibiotic and antifungal compound development.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"37"},"PeriodicalIF":2.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placental mesenchymal stem cell-derived exosomes treat endometrial injury in a rat model of intrauterine adhesions.","authors":"Lin Liang, Huidong Liu, Shaowei Wang","doi":"10.1007/s00438-025-02241-x","DOIUrl":"10.1007/s00438-025-02241-x","url":null,"abstract":"<p><p>Intrauterine adhesion (IUA) refer to persistent inflammation and fibrosis due to damaged or infected endometrium and eventually lead to dysfunction. This study aimed to explore the therapeutic effects of exosomes (Exos) derived from placental mesenchymal stem cells (PMSCs) on endometrial repair in a rat model of IUA and to elucidate the underlying molecular mechanisms. PMSCs were characterized using flow cytometry and differentiation assays (osteogenic, adipogenic, and chondrogenic). Exos were isolated via ultracentrifugation and validated through transmission electron microscopy, nanoparticle tracking analysis and Western blot. An IUA model was established via electrocoagulation, and endometrial repair was assessed using hematoxylin-eosin (HE) and Masson staining. RNA sequencing, differential expression analysis and protein-protein interaction (PPI) network construction were employed to investigate the molecular mechanisms of PMSC Exos mediated repair. The role of miR-143 in targeting MyD88 and modulating the NF-κB signaling pathway was confirmed using Dual-Luciferase Reporter Assay and qRT-PCR. PMSC Exos significantly improved endometrial thickness, increased glandular number and reduced fibrosis in the IUA model. RNA sequencing and differential expression analysis screened 3980 differentially expressed genes (DEGs) common to the IUA vs normal groups and Exo vs IUA groups. Enrichment analysis revealed significant involvement of immune system processes, natural killer cell-mediated cytotoxicity and NF-κB signaling. PMSC Exos delivered miR-143, which targeted MyD88, thereby regulating the NF-κB pathway. PMSC Exos effectively repaired endometrial damage in the IUA model by modulating the NF-κB signaling pathway through miR-143 delivery. These findings suggest that PMSC Exos hold promise as a novel therapeutic strategy for IUA, offering insights into the molecular mechanisms underlying endometrial repair.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"36"},"PeriodicalIF":2.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700951","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":"Computational insights into host-pathogen protein interactions: unveiling penaeid shrimp and white spot syndrome virus interplay.","authors":"Nimisha Kaikkolante, Vinaya Kumar Katneni, Gangaraj Karyath Palliyath, Ashok Kumar Jangam, Jagabattulla Syamadayal, Karthic Krishnan, Sudheesh Kommu Prabhudas, Mudagandur Shashi Shekhar","doi":"10.1007/s00438-025-02242-w","DOIUrl":"https://doi.org/10.1007/s00438-025-02242-w","url":null,"abstract":"<p><p>White spot syndrome virus (WSSV) has been a major threat in shrimp farming system especially for penaeid shrimps. The lack of effective control measures for WSSV makes this disease a significant threat to aquaculture. This study seeks to explore the mechanisms of WSSV infection and its impact on shrimp by examining host-pathogen interactions (HPI) through in silico approach, which can offer valuable insights into the processes of infection and disease progression. The investigation focused on five Penaeus species, including Penaeus vannamei, Penaeus chinensis, Penaeus monodon, Penaeus japonicus, and Penaeus indicus, studying their interaction with the WSSV. This study employed orthology-based and domain-driven analyses to reveal protein-protein interactions (PPIs) between the host and the pathogen. The combined strategies were found to be effective in detecting shared molecular mechanisms in pathogenesis, unveiling intricate PPI networks critical for virulence and host response. Most interacting proteins in WSSV are immediate early proteins involved in DNA replication and proliferation, and are crucial for ubiquitination, transcription regulation, and nucleotide metabolism. A large number of host proteins interact with WSSV across species (2360-11,704 interactions), with P. chinensis (11,704) and P. japonicus (11,458) exhibiting the highest counts, suggesting greater susceptibility or response. Host hub proteins are crucial in signaling, cellular processes, and metabolism, interacting across the cytoplasm, nucleus, and membrane, highlighting their role in WSSV pathogenesis. This study provides essential insights into host-pathogen interactions, offering a foundation for future research aimed at improving WSSV control in shrimp aquaculture.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"35"},"PeriodicalIF":2.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyphenols as microRNA modulator in endometrial cancer: implications for apoptosis induction.","authors":"Dan Liu, Xiaohua Liu","doi":"10.1007/s00438-025-02238-6","DOIUrl":"https://doi.org/10.1007/s00438-025-02238-6","url":null,"abstract":"<p><p>Endometrial cancer (EC) accounts for approximately 417,336 cases globally, making it the sixth most commonly diagnosed cancer among women. Such factors have led to hesitancy in utilizing aggressive treatments or enrolling older patients in clinical trials. Recent molecular studies have identified unique expression patterns of microRNAs (miRNAs) in endometrial cancer tissue compared to healthy endometrial tissue, highlighting their role in tumorigenesis through pathways that support proliferation, invasion, and metastasis. Polyphenols, bioactive compounds found in a variety of plant-based foods such as fruits, vegetables, tea, and soybeans, have demonstrated diverse physiological benefits, including antioxidant, anti-inflammatory, and anticancer properties. These compounds influence cellular pathways critical to cancer progression, including apoptosis, immune modulation, and inflammation reduction. Emerging evidence suggests that polyphenols may exert anticancer effects in part by modulating miRNAs involved in carcinogenesis. Specifically, compounds like curcumin, quercetin, resveratrol, and genistein have shown potential in targeting oncogenic and tumor-suppressive miRNAs, thereby impacting cellular mechanisms linked to cancer progression. Therefore, this review examines the role of polyphenols in regulating miRNAs within the context of endometrial cancer, focusing on their potential to modulate apoptosis and other cancer hallmarks. By elucidating these mechanisms, this paper aims to contribute to the understanding of polyphenol-mediated miRNA regulation as a promising therapeutic avenue in endometrial cancer management.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"34"},"PeriodicalIF":2.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular epidemiological study of Pseudomonas aeruginosa strains isolated from hospitals in Brazil by MLST and CRISPR/Cas system analysis.","authors":"Keyla Vitória Marques Xavier, Ana Carolina de Oliveira Luz, José Wilson Silva-Junior, Beatriz Souza Toscano de Melo, Marcus Vinícius de Aragão Batista, Adrianne Maria de Albuquerque Silva, Valdir de Queiroz Balbino, Tereza Cristina Leal-Balbino","doi":"10.1007/s00438-025-02239-5","DOIUrl":"10.1007/s00438-025-02239-5","url":null,"abstract":"<p><p>The CRISPR/Cas system defends bacteria and archaea against invasive pathogens, such as phages, establishing an immunological memory from this interaction. Pseudomonas aeruginosa, an opportunistic pathogen, represents a significant public health concern due to its multidrug resistance. This study conducted a molecular epidemiological analysis of clinical isolates of Pseudomonas aeruginosa in Brazil using multilocus sequence typing (MLST) and characterization of CRISPR/Cas system. Most P. aeruginosa isolates harbored the type I-F CRISPR/Cas system (83%), with a subset also exhibiting the type I-E system. Additionally, some isolates presented incomplete CRISPR/Cas systems in their secondary loci. Notably, the isolate Pae93 exhibited a genetic composition rich in phage-related proteins proximal to the orphan CRISPR locus. The identification and characterization of spacer sequences, including previously undocumented ones, revealed a remarkable diversity of predatory mobile genetic elements (MGEs) among the P. aeruginosa isolates studied. The spacer sequences were incorporated into the MGE library. Additionally, the study identified the existence of prophages and anti-CRISPR genes. Two new sequence types (STs 3383 and 3384) were identified and added to the PubMLST database. No discernible correlation was established between the observed STs and the previously delineated CRISPR genotypes. However, the CRISPR system remains valuable for elucidating specific interactions between microorganisms and MGEs. The Brazilian population of clinical P. aeruginosa isolates was shown to be genetically heterogeneous with a non-clonal distribution, as revealed by MLST analysis. The presence of high-risk clones, such as ST 244 and ST 235, underscores the importance of robust epidemiological surveillance and infection control strategies for P. aeruginosa, especially in healthcare settings. This study significantly contributes to the understanding of the molecular epidemiology of these isolates in Brazil.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"33"},"PeriodicalIF":2.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670507","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":"Developing a genome-wide long sequence-specific tag for sex identification in spotted knifejaw (Oplegnathus punctatus).","authors":"Pingrui Xu, Yongshuang Xiao, Zhizhong Xiao, Jun Li","doi":"10.1007/s00438-025-02240-y","DOIUrl":"https://doi.org/10.1007/s00438-025-02240-y","url":null,"abstract":"<p><p>Spotted knifejaw (Oplegnathus punctatus), an economically important species in marine aquaculture, employs a unique sex determination mechanism based on a complex sex chromosome system (X₁X₁X₂X₂/X₁X₂Y). Males (2n = 47) possess one fewer chromosome than females (2n = 48), and their karyotype includes an unusually large neo-Y chromosome. Additionally, a pronounced sexual dimorphism in growth rate is observed, with males exhibiting a faster growth rate than females. In this study, we conducted a comprehensive whole-genome scan, which initially revealed structural variations in the anti-inflammatory itih4 gene between male and female O. punctatus. Additionally, we designed a pair of primers to detect DNA sequence variations within the itih4a/itih4b gene. These variations are located in the intergenic region of the fusion Y chromosome in male O. punctatus, compared to the homologous X chromosome in females. In females without DNA insertions in the itih4a/itih4b intergenic region, a single band of 351 bp is amplified. By contrast, in males with DNA insertions, two bands are amplified (755 bp and 351 bp). The 755 bp band specifically indicates the presence of a DNA insertion in the itih4a/itih4b intergenic region on the Y chromosome, associated with male-specific genetic traits. Our study will facilitate the rapid identification of the genetic sex of both male and female O. punctatus individuals.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"32"},"PeriodicalIF":2.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of a prognostic risk model for clear cell renal cell carcinomas based on centrosome amplification-related genes.","authors":"Bingru Zhou, Fengye Liu, Ying Wan, Lin Luo, Zhenzhong Ye, Jinwei He, Long Tang, Wenzhe Ma, Rongyang Dai","doi":"10.1007/s00438-025-02237-7","DOIUrl":"10.1007/s00438-025-02237-7","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC) is the urological malignancy with the highest incidence, centrosome amplification-associated genes (CARGs) have been suggested to be associated with carcinogenesis, but their roles in ccRCC are still incompletely understood. This study utilizes bioinformatics to explore the role of CARGs in the pathogenesis of ccRCC and to establish a prognostic model for ccRCC related to CARGs. Based on publicly available ccRCC datasets, 2312 differentially expressed genes (DEGs) were identified (control vs. ccRCC). Disease samples were classified into high and low scoring groups based on CARG scores and analysed for differences to obtain 345 DEGs associated with CARG scores (S-DEGs). 137 candidate genes were obtained by taking the intersection of DEGs and S-DEGs. Six prognostic genes (PCP4, SLN, PI3, PROX1, VAT1L, and KLK2) were then screened by univariate Cox, LASSO, and multifactorial Cox regression. These genes exhibit a high degree of enrichment in ribosome-associated pathways. Both risk score and age were independent prognostic factors, and the Nomogram constructed based on them had a good predictive performance (AUC > 0.7). In addition, immunological analyses identified 6 different immune cells and 23 immune checkpoints between the high- and low-risk groups, whereas mutational analyses identified frequent VHL mutations in both high- and low-risk groups. Finally, 93 potentially sensitive drugs were identified. In conclusion, this study identified six CARGs as prognostic genes for ccRCC and established a risk model with predictive value. These findings provide insights for prognostic prediction of ccRCC, optimisation of clinical management and development of targeted therapeutic strategies.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"30"},"PeriodicalIF":2.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616226","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":"Proto-oncogene DEK binds to pre-mRNAs and regulates the alternative splicing of Hippo signaling genes in HeLa cells.","authors":"Dongbo Liu, Wei Sun, Jing Han, Cong Wang, Dong Chen, Yunfei Wu, Yongjie Chang, Bin Yang","doi":"10.1007/s00438-025-02226-w","DOIUrl":"10.1007/s00438-025-02226-w","url":null,"abstract":"<p><p>Our study aimed to explore how DEK, a carcinogenic protein with chromatin architectural function, genome-widely binds to RNA and affects the alternative splicing in cancer cells to decipher its molecular functions. To achieve this goal, cell phenotype experiments, RNA sequencing (RNA-seq), and improved RNA immunoprecipitation sequencing (iRIP-seq) were conducted to identify the function and regulated targets of DEK in HeLa cells. The results showed DEK overexpression promoted cell proliferation and invasion of HeLa cells. Meanwhile, DEK hardly affected transcript level expression of those high expressed genes, but splicing pattern of 411 genes was regulated by DEK in HeLa cells, which were enriched in Hippo signaling pathway. Moreover, DEK broadly bind the RNA of a total of 11, 112 genes, with a biased binding the 5' splice site (5'SS) consensus GGUAA motifs at the CDS and intronic regions. In addition, 297 DEK-binding genes showed different splicing pattern after DEK overexpression in HeLa cells. These genes were enriched in Hippo signaling pathway including CSNK1D. The RT-qPCR and RIP-PCR confirmed that DEK can bind to CSNK1D to regulate its alternative splicing in HeLa cells. In summary, our results indicated DEK could broadly bind and regulate the pre-mRNA splicing process, which provide new insights of mechanisms that DEK functions in various biological processes including cancer.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"31"},"PeriodicalIF":2.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616234","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 molecular spectrum of thalassemia in infertile population among different ethnic groups in Hainan Province, China.","authors":"Yongle Zhang, Jinyu Kang, Wenye Sun, Fei Sun, Ge Gao, Junhong Chen, Qi Li, Qiuling Jie, Yanlin Ma","doi":"10.1007/s00438-025-02234-w","DOIUrl":"https://doi.org/10.1007/s00438-025-02234-w","url":null,"abstract":"<p><p>Hainan is an area with high prevalence of thalassemia and complex genetic background. There are few studies on the prevalence and genotype of thalassemia in different ethnic groups of infertility patients in Hainan province. The aim of our study was to explore the prevalence and genotype of thalassemia among infertile individuals in Hainan Province. Thalassemia genotypes were determined using gap-PCR and PCR-RBD in 13,856 infertile individuals in our study. Among them, 3458 (24.96%) were diagnosed as thalassemia carriers. In Li ethnic group, 649 (75.12%) were diagnosed as thalassemia carriers, which significantly higher than Han (21.62%) and other ethnicities (22.09%). As the molecular spectrum of thalassemia, the most common α-thalassemia genotype among Han and other ethnicities was -α^3.7/αα, while among Li ethnic group was -α^4.2/αα. For β-thalassemia, the most common genotype among Han and Li ethnic groups was β^41-42 M/βN, while both β^41-42 M/βN and β^17M/βN were common genotype in other ethnic groups. In αβ-complex thalassemia, the most common genotype among the Han ethnic group was -α^3.7/αα & β^41-42 M /βN, followed by -α^4.2/αα & β^41-42 M /βN in the Li ethnic group, and αα^WS/αα & β^41-42 M /βN and -α^4.2/αα & β^41-42 M /β^17M were common in other ethnic groups. Compare with reproductive age population, the infertile population in our study exhibits a notably higher prevalence of α-thalassemia carriers, particularly those with the silent type. This study reveals the genetic epidemiology of thalassemia in the region, providing a scientific basis for targeted health interventions, screening programs, and genetic counseling for infertile population in Hainan Province.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"29"},"PeriodicalIF":2.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trio-WES and functional validation reveals a novel splice site variant of SLC26A3 in a case with congenital chloride diarrhea and a systematic review of SLC26A3 mutations in China.","authors":"Ruixue Zhang, Hongping Li, Rong Qiang, XinRu Gao, Jinzhen Guo, Guoqiang Chen, Qin Nan, Limei Zhong, Lin Wang","doi":"10.1007/s00438-025-02233-x","DOIUrl":"https://doi.org/10.1007/s00438-025-02233-x","url":null,"abstract":"<p><p>Congenital chloride diarrhea (CCD) is an autosomal recessive disease, characterized by watery diarrhea, hypochloremia and metabolic alkalosis. It is associated with defects in solute carrier family 26 member 3 (SLC26A3) which acts as Na⁺-independent Cl^-/HCO₃^- exchanger. Early diagnosis allows planning of perinatal care and timely treatment to improve the prognosis of CCD. However, only few cases were diagnosed in the fetus period, while most of CCD cases were diagnosed after birth without timely diagnosis and treatment. This study was conducted to verify the disease-causing gene by prenatal genetic and functional tests for assisting prenatal diagnosis of a fetus with suspected CCD and reviewed the mutation spectrum of Chinese CCD patients for the first time. Here, we reported a suspected CCD fetus with signs of polyhydramnios and intestinal dilatation by prenatal ultrasound. Subsequent prenatal Trio-whole-exome sequencing identified a novel homozygous mutation (c.383-5A > G) of SLC26A3, which was classified as uncertain significance (VUS). Mini-Gene Splicing Assay confirmed the effect of VUS variant on abnormal splicing of SLC26A3, increasing pathogenicity evidence, and determining the prenatal diagnosis and subsequent treatment of CCD. Literature review of 18 CCD cases showed that t c.270_271insAA (p.G91Kfs*3) was the most frequent mutation in China. In conclusion, our study found the novel c.383-5A > G mutation of SLC26A3 as the pathogenic cause in the proband, which expanded the mutation spectrum of SLC26A3. There also highlights the importance of integrative genetic and functional tests that provide a reference for prenatal diagnosis of suspected CCD to access postnatal management in a timely manner.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"300 1","pages":"28"},"PeriodicalIF":2.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}