Human Genomics最新文献

{"title":"Establishment and validation of a DIP panel for forensic ancestry inference and personal identification.","authors":"Shuanglin Li, Shuyan Mei, Yanfang Liu, Wei Cui, Bofeng Zhu","doi":"10.1186/s40246-025-00727-8","DOIUrl":"10.1186/s40246-025-00727-8","url":null,"abstract":"<p><strong>Background: </strong>Biallelic Deletion/Insertion polymorphisms (DIPs), known for their significant diversity across various populations, serve as valuable markers for forensic ancestry inference and personal identification. In this study, we utilized DIPs to provide a potentially powerful forensic examination tool specifically tailored for East Asian populations. Our focus on ancestry allows us to delve deeper into the genetic signatures that characterize this diverse group, offering enhanced resolution in forensic analyses.</p><p><strong>Methods: </strong>A total of 56 autosomal DIPs, 3 Y-chromosome DIPs, and the Amelogenin were selected to build the 60-panel. Population genetic parameters, principal component analysis (PCA), STRUCTURE analysis, and phylogenetic tree construction were employed to evaluate the capacity for ancestry inference. The verification guidelines recommended by the Scientific Working Group on DNA Analysis Methods were followed in the developmental validations of the 60-panel.</p><p><strong>Results: </strong>The PCA, STRUCTURE, and phylogenetic tree constructions were not only consistent with each other but also corroborated by previous research. The combined probability of discrimination and the cumulative probability of paternity exclusion values were 0.999999999999 and 0.9937, respectively. These values indicate that the 60-panel is not only a useful tool for personal identification testing within the East Asian population but also provides valuable biogeographic information. Furthermore, the validation study of the 60-panel, which included assessments of PCR conditions, sensitivity, species specificity, stability, mixture analysis, reproducibility, and case sample studies, as well as analysis of degraded samples, demonstrated that the panel is well-suited for forensic testing. The panel's performance was particularly notable in the analysis of degraded samples, showcasing its potential for use in challenging forensic cases.</p><p><strong>Conclusion: </strong>The newly developed 60-panel demonstrated robust performance in validation tests, yielding reliable genotypes even from poor-quality samples like degraded DNA. It offers valuable biogeographic insights and sufficient polymorphism for personal identification, which assisted forensic examinations in East Asian populations.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"30"},"PeriodicalIF":3.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying behavior regulatory leverage over mental disorders transcriptomic network hubs toward lifestyle-dependent psychiatric drugs repurposing.","authors":"Mennatullah Abdelzaher Turky, Ibrahim Youssef, Azza El Amir","doi":"10.1186/s40246-025-00733-w","DOIUrl":"10.1186/s40246-025-00733-w","url":null,"abstract":"<p><strong>Background: </strong>There is a vast prevalence of mental disorders, but patient responses to psychiatric medication fluctuate. As food choices and daily habits play a fundamental role in this fluctuation, integrating machine learning with network medicine can provide valuable insights into disease systems and the regulatory leverage of lifestyle in mental health.</p><p><strong>Methods: </strong>This study analyzed coexpression network modules of MDD and PTSD blood transcriptomic profile using modularity optimization method, the first runner-up of Disease Module Identification DREAM challenge. The top disease genes of both MDD and PTSD modules were detected using random forest model. Afterward, the regulatory signature of two predominant habitual phenotypes, diet-induced obesity and smoking, were identified. These transcription/translation regulating factors (TRFs) signals were transduced toward the two disorders' disease genes. A bipartite network of drugs that target the TRFS together with PTSD or MDD hubs was constructed.</p><p><strong>Results: </strong>The research revealed one MDD hub, the CENPJ, which is known to influence intellectual ability. This observation paves the way for additional investigations into the potential of CENPJ as a novel target for MDD therapeutic agents development. Additionally, most of the predicted PTSD hubs were associated with multiple carcinomas, of which the most notable was SHCBP1. SHCBP1 is a known risk factor for glioma, suggesting the importance of continuous monitoring of patients with PTSD to mitigate potential cancer comorbidities. The signaling network illustrated that two PTSD and three MDD biomarkers were co-regulated by habitual phenotype TRFs. 6-Prenylnaringenin and Aflibercept were identified as potential candidates for targeting the MDD and PTSD hubs: ATP6V0A1 and PIGF. However, habitual phenotype TRFs have no leverage over ATP6V0A1 and PIGF.</p><p><strong>Conclusion: </strong>Combining machine learning and network biology succeeded in revealing biomarkers for two notoriously spreading disorders, MDD and PTSD. This approach offers a non-invasive diagnostic pipeline and identifies potential drug targets that could be repurposed under further investigation. These findings contribute to our understanding of the complex interplay between mental disorders, daily habits, and psychiatric interventions, thereby facilitating more targeted and personalized treatment strategies.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"29"},"PeriodicalIF":3.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serine/threonine kinase 11 (STK11) associated adnexal tumors: from biology to therapeutic impact.","authors":"Guanxiang Huang, Wenyu Lin, Tingting Jiang, Yuanjun Cai, Chengbin Lin, Pengming Sun","doi":"10.1186/s40246-025-00741-w","DOIUrl":"10.1186/s40246-025-00741-w","url":null,"abstract":"<p><p>Female adnexal malignancies, while relatively uncommon, exhibit high mortality rates due to often-late diagnosis. The serine/threonine kinase 11 (STK11) is a tumor suppressor gene, and its inactivation or mutation often leads to an autosomal dominant genetic disorder known as Peutz-Jeghers syndrome (PJS), which is associated with ovarian and cervical cancers. STK11-associated adnexal tumors mostly originate from the ovary, with a low incidence rate but high metastasis rates worldwide. In addition to surgery and chemotherapy, it is necessary to optimize relevant screening policy and targeted therapy. STK11-associated adnexal tumors are difficult to diagnose by histopathology. Although genetic testing involves higher costs, it can serve as a primary preventive measure for high-risk populations with STK11-associated tumors. A more intensive screening program (MISP) is needed for individuals with significant clinical symptoms and a family history of PJS. These tumors may be adequately treated with fertility-sparing surgery in young women with lower malignant potential tumors. Prophylactic adnexectomy, chemotherapy, and immunotherapy may offer potential clinical benefits but also pose significant challenges. Therefore, surgery should be undertaken with careful and comprehensive consideration of the patient's age, reproductive history, risk of malignancy, genetic mutation lineages, post-operative complications, and other conditions. Further research is essential to develop better screening, diagnostic, and treatment strategies.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"28"},"PeriodicalIF":3.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic profiling of Cell-free DNA fragmentation uncovers postprandial metabolic and immune alterations.","authors":"Ziting Zhu, Tao Chen, Manting Zhang, Xiaodi Shi, Pan Yu, Jianai Liu, Xiuzhi Duan, Zhihua Tao, Xuchu Wang","doi":"10.1186/s40246-025-00739-4","DOIUrl":"10.1186/s40246-025-00739-4","url":null,"abstract":"<p><strong>Background: </strong>Food intake affects body homeostasis and significantly changes circulating cell-free DNA (cfDNA). However, the source and elimination of postprandial cfDNA is difficult to trace, and it is unknown whether these changes can be revealed by cfDNA fragmentomics based on liquid biopsy.</p><p><strong>Methods: </strong>We performed shallow whole-genome sequencing of 30 plasma samples from 10 healthy individuals at fasting and postprandial (30-min and 2-h time points). We assessed the effect of postprandial states on cfDNA fragment size distribution and utilized deconvolutional analysis of end motifs to determine the potential roles of DNA nucleases in cfDNA fragmentation. We correlated the fragmentation index (defined as the ratio of short-to-long fragments) with gene expression to estimate the relative contribution of various cellular and tissue sources to cfDNA.</p><p><strong>Results: </strong>Compared to the fasting state, we observed a significant increase in short cfDNA fragments (70-150 bp) and a decrease in long fragments (151-250 bp) at the 30-minute postprandial state, followed by an inverse trend two hours later. Deconvolutional analysis of cfDNA end motifs showed that DNASE1L3 activity decreased at the 30-minute postprandial state, while DNASE1 and DFFB activities increased at the 2-hour postprandial state. We found that the expression of genes related to cellular metabolism and immune responses was upregulated at the postprandial state. Meanwhile, the contribution of cells and tissues involved in metabolic and immune progress to circulating plasma cfDNA was increased.</p><p><strong>Conclusions: </strong>The fragmentation of cfDNA is considerably influenced by postprandial states, highlighting the significance of taking postprandial effects into account when evaluating cfDNA as a biomarker. Furthermore, our study reveals the potential application of cfDNA fragmentation features in monitoring metabolic and immune status changes.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"27"},"PeriodicalIF":3.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adults.","authors":"Xiayin Zhang, Shan Wang, Shunming Liu, Zijing Du, Guanrong Wu, Yingying Liang, Yu Huang, Xianwen Shang, Yijun Hu, Zhuoting Zhu, Wei Sun, Xueli Zhang, Honghua Yu","doi":"10.1186/s40246-025-00737-6","DOIUrl":"10.1186/s40246-025-00737-6","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"26"},"PeriodicalIF":3.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The CFTR K464N variant in fetuses potential increases premature birth risk in Chinese families.","authors":"Jingping Li, Lingyun Zhang, Fangfang Xi, Chuanping Lin, Qitao Zhan, Qing Zhou, Shi Zheng, Weikang Chen, Fan Jin","doi":"10.1186/s40246-025-00736-7","DOIUrl":"10.1186/s40246-025-00736-7","url":null,"abstract":"<p><strong>Background: </strong>Global fertility decline has led to increased use of assisted reproductive technology (ART), raising concerns about genetic risks to offspring. This study aimed to investigate cystic fibrosis transmembrane conductance regulator (CFTR) variants in Chinese families and assess their association with pregnancy complications and neonatal outcomes.</p><p><strong>Methods: </strong>This prospective cohort study included 446 Chinese families (148 natural conceptions, 298 ART conceptions) who underwent whole genome sequencing. We analyzed the frequency of pathogenic/likely pathogenic CFTR variants and their association with preterm birth (PTB), pregnancy complications, and neonatal outcomes.</p><p><strong>Results: </strong>Twelve pathogenic/likely pathogenic CFTR variants were identified, with K464N (c.1392G > T) being the most prevalent (2.9% of cohort). PTB incidence was significantly higher in pregnancies with fetal CFTR variants (43.1%, 22/51) compared to those without (17.5%, 69/395; p < 0.001). Fetuses carrying the CFTR K464N variant exhibited a 3.39-fold increased risk of PTB (95% confidence interval (CI): 1.39-8.23, p = 0.007) after adjusting for confounders. Neither fetal nor maternal CFTR variants were significantly associated with other neonatal outcomes, including neonatal weight, Apgar scores, respiratory distress, or hyperbilirubinemia (p > 0.050).</p><p><strong>Conclusion: </strong>These findings suggest a potential association between fetal CFTR K464N variant and increased risk of preterm birth in Chinese families, highlighting the importance of considering CFTR genotyping in prenatal care.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"25"},"PeriodicalIF":3.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishing a European wastewater pathogen monitoring network employing aviation samples: a proof of concept.","authors":"Robert Morfino, Bernd Manfred Gawlik, Simona Tavazzi, Angela Tessarolo, Ana Burgos Gutierrez, Nita K Madhav, Jasmine Grimsley, Amy Schierhorn, Andrew Franklin, Marta Vargha, Andrew Engeli, Mitchell Wolfe","doi":"10.1186/s40246-025-00725-w","DOIUrl":"10.1186/s40246-025-00725-w","url":null,"abstract":"<p><p>Pathogens know no borders, and the COVID-19 pandemic highlighted the urgent need for comparable, globally accessible pathogen data. This paper proposes a European wastewater pathogen monitoring network using aircraft and airport samples as a proof of concept for an effective cross-national surveillance system. The study emphasizes the importance of genomic data collection from strategic sites to produce high-value data for disease surveillance and epidemiological analysis. The authors suggest establishing \"Super Sites\" in key locations, particularly major transportation hubs like airports, to serve as focal points for wastewater-based pathogen surveillance. The European Commission has identified over 20 candidate Super Sites and supports their integration into a Global Wastewater Sentinel System. In October 2023, the European Commission's Joint Research Centre (JRC) and Ginkgo Bioworks conducted an ad hoc exercise, collecting and analyzing wastewater samples from airports and aircraft across Europe. This exercise demonstrated the feasibility of coordinated sampling, centralized processing, and data sharing across different countries. Samples were collected from eight airports over two weeks, employing various methods for different types of wastewater, including samples from terminals and aircraft. Across airports, 96% of wastewater samples tested positive for SARS-CoV-2, with similar viral loads between aircraft and airport sewage, and multiple lineages were identified, including the EG.5 variant, which is consistent with the publicly reported variant data. The results underscore the potential of routine aircraft wastewater monitoring as an early warning system for emerging pathogens. The study also highlights the need for standardized protocols and real-time reporting systems and the importance of addressing ethical considerations in handling passenger data. By creating a network of Super Sites, and integrating cross-national wastewater surveillance data with passenger flight data, the European Union aims to strengthen global public health responses to future pandemics. Establishing this surveillance network is a crucial step towards a pan-European surveillance system for pathogens, providing a non-intrusive complement to existing systems that rely on individual testing. This system will significantly improve early detection capabilities, leading to more rapid and robust responses and ultimately enhancing global health security.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"24"},"PeriodicalIF":3.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the silent connection: unveiling the intricate relationship between gastroesophageal reflux disease and sleep apnea syndrome.","authors":"Junming Wang, Pengfei Wang, Jiang Lv, Ran Chen, Wei Yan, Daikun He","doi":"10.1186/s40246-025-00728-7","DOIUrl":"10.1186/s40246-025-00728-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Gastroesophageal reflux disease (GERD) and Sleep Apnea Syndrome (SAS) are two prevalent medical conditions that significantly affect health and quality of life. GERD involves stomach content reflux into the esophagus, while SAS causes recurrent upper airway obstruction during sleep. Despite recent studies hinting at a link, the precise relationship and causality between GERD and SAS remain unclear. Our research uses bidirectional Mendelian randomization to explore this intricate relationship. Additionally, given SAS's high prevalence in cardiovascular patients (40-80%, as highlighted by the American Heart Association), we also investigated its potential association with various cardiovascular diseases to gain new insights into prevention and treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study employed genetic data from large-scale genome-wide association studies (GWAS) on GERD (129,080 cases, 473,524 controls) and SAS (25,008 cases, 391,473 controls) for two-sample Mendelian randomization (MR) analysis to estimate the causal effects of GERD on the risk of SAS. All SNPs were selected using a strict clump window (r&lt;sup&gt;2&lt;/sup&gt; = 0.001 and kb = 10,000). We initially applied the inverse variance weighted (IVW) method and measured horizontal pleiotropy using MR-Egger, weighted median, and weighted mode methods. I&lt;sup&gt;2&lt;/sup&gt; index and Cochran Q statistics were used for sensitivity analysis. Funnel plot symmetry of IVW MR estimates versus 1/standard error (1/SEIV) was examined to exclude SNPs potentially causing heterogeneity. Additionally, to exclude reverse causality, bidirectional MR was employed to investigate whether genetic susceptibility to SAS causally influenced the risk of GERD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;GERD was associated with an elevated risk of SAS, demonstrating an odds ratio (OR) of 1.750 (95% CI 1.590-1.930; P &lt; 0.001). Conversely, there was no compelling evidence to indicate a causal link between SAS and the risk of developing GERD, with an OR of 1.000 (95% CI 0.989-1.011; P = 0.964). In addition to the primary findings, our study also revealed significant risks associated with SAS for several cardiovascular conditions, including coronary heart disease, atrial fibrillation, coronary artery disease, heart failure, intracerebral hemorrhage, and ischemic stroke.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;We discovered compelling evidence indicating an elevated risk of SAS in individuals with GERD, but no significant evidence supporting an increased risk of GERD in those with SAS. Future investigations into SAS risk should take into account the potential therapeutic targeting of GERD. PPI and histamine antagonists can effectively reduce reflux and airway secretions, preventing airway damage and collapse. Furthermore, it is necessary to investigate the underlying mechanisms by which GERD affects SAS. For example, the inflammatory stimulation caused by gastric acid and pepsin in refluxed fluid, as well as the","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"23"},"PeriodicalIF":3.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic landscape and ocular biometric correlations in microspherophakia: insights from a comprehensive patient cohort.","authors":"Yan Liu, Yang Sun, Qiuyi Huo, Linghao Song, Xinyue Wang, Xin Shen, Ye Zhao, Tianhui Chen, Yongxiang Jiang","doi":"10.1186/s40246-025-00729-6","DOIUrl":"10.1186/s40246-025-00729-6","url":null,"abstract":"<p><strong>Aims: </strong>The aim of this study is to elucidate the genetic landscape of microspherophakia (MSP) and describe the genotype-phenotype correlation of MSP. Additionally, the study seeks to enhance the understanding of the pathogenic mechanisms of MSP through the discovery of novel loci.</p><p><strong>Methods: </strong>Patients diagnosed with MSP at the Eye and ENT Hospital of Fudan University, Shanghai, were included in the study and all underwent panel-based next-generation sequencing and bioinformatics analysis. Comprehensive ophthalmologic evaluations were conducted for each participant.</p><p><strong>Results: </strong>Our analysis encompassed 118 eyes from 59 patients with MSP, revealing 13 gene variations linked to the condition. Notably, FBN1 mutations were identified in 31 patients (52.5%), highlighting its higher prevalence. Among the genetic variations discovered, 28 represented novel mutations. Statistical analysis unveiled significant associations between specific gene mutations and ocular biometric parameters: axial length (AL, p = 0.011), Z-score axial length (Z-AL, p < 0.001), white-to-white (WTW, p = 0.009), Z-score white-to-white (p = 0.012), mean keratometry (p < 0.001), astigmatism (AST, p = 0.021), anterior chamber depth (ACD, p = 0.003), lens thickness (LT, p = 0.012) and central endothelial cell count/mm2 (p = 0.005). Patients with FBN1 mutations had the longest AL, while those with CBS mutations showed significantly wilder WTW measurements. Patients with ADAMTS17 mutations presented with increased LT and decreased WTW, ADAMTSL4 mutations were linked to the greater Km and AST. Patients with LTBP mutations exhibited the largest WTW, and ASPH mutations was associated with the shortest AL but thick LT. Additionally, there was a relationship among gene mutations, diagnostic age and ocular biometric parameters.</p><p><strong>Conclusion: </strong>The study demonstrates that MSP is associated with a diverse range of genetic mutations, with FBN1 being the most common. Novel mutations were identified, and significant correlations were found between specific genetic variations and ocular biometric parameters. These results provide new insights into the genetic underpinnings of MSP and its clinical characteristics, advancing our understanding of the condition's pathogenic mechanisms.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"22"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sengers syndrome caused by biallelic TIMM29 variants and RNAi silencing in Drosophila orthologue recapitulates the human phenotype.","authors":"Adel Shalata, Ann Saada, Mohammed Mahroum, Yarin Hadid, Chaya Furman, Zaher Eldin Shalata, Robert J Desnick, Avraham Lorber, Asaad Khoury, Adnan Higazi, Avraham Shaag, Varda Barash, Ronen Spiegel, Euvgeni Vlodavsky, Pierre Rustin, Shmuel Pietrokovski, Irena Manov, Dan Gieger, Galit Tal, Adi Salzberg, Hanna Mandel","doi":"10.1186/s40246-025-00723-y","DOIUrl":"10.1186/s40246-025-00723-y","url":null,"abstract":"<p><strong>Purpose: </strong>Sengers-syndrome (S.S) is a genetic disorder characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy and lactic acidosis. All reported cases were genetically caused by biallelic mutations in the AGK gene. We herein report a pathogenic variant in TIMM29 gene, encoding Tim29 protein, as a novel cause of S.S. Notably, AGK and Tim29 proteins are components of the TIM22 complex, which is responsible for importing carrier proteins into the inner mitochondrial membrane.</p><p><strong>Method: </strong>Clinical data of 17 consanguineous patients featuring S.S was obtained. Linkage analysis, and sequencing were used to map and identify the disease-causing gene. Tissues derived from the study participants and a Drosophila melanogaster model were used to evaluate the effects of TIMM29 variant on S.S.</p><p><strong>Results: </strong>The patients presented with a severe phenotype of S.S, markedly elevated serum creatine-phosphokinase, combined mitochondrial-respiratory-chain-complexes deficiency, reduced pyruvate-dehydrogenase complex activity, and reduced adenine nucleotide translocator 1 protein. Histopathological studies showed accumulation of abnormal mitochondria. Homozygosity mapping and gene sequencing revealed a biallelic variant in TIMM29 NM_138358.4:c.514T > C NP_612367.1:p.(Trp172Arg). The knockdown of the Drosophila TIMM29 orthologous gene (CG14270) recapitulated the phenotype and pathology observed in the studied cohort. We expand the clinical phenotype of S.S and provide substantial evidence supporting TIMM29 as the second causal gene of a severe type of S.S, designated as S.S- TIMM29.</p><p><strong>Conclusion: </strong>The present study uncovers several biochemical differences between the two S.S types, including the hyperCPKemia being almost unique for S.S-TIMM29 cohort, the different frequency of MMRCC and PDHc deficiencies among the two S.S types. We propose to designate the S.S associated with TIMM29 homozygous variant as S.S-TIMM29.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"21"},"PeriodicalIF":3.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}