BMC Medical Genomics最新文献

{"title":"Genomic determinants of fluoroquinolone resistance in Escherichia coli in Nigeria: dominance of QRDR mutations and limited contribution of PMQR in a cross-sectional study.","authors":"Nubwa Medugu, Mabel Kamweli Aworh, Khadija Abdulraheem, Dawn M Hull, Lyndy Harden, Siddhartha Thakur","doi":"10.1186/s12920-026-02396-5","DOIUrl":"10.1186/s12920-026-02396-5","url":null,"abstract":"<p><strong>Background: </strong>Fluoroquinolone-resistant Escherichia coli is a major global clinical threat, particularly in low- and middle-income countries like Nigeria. However, the full genomic landscape, including the relative contributions of chromosomal mutations, plasmid-mediated resistance, and the role of high-risk clones, remains poorly characterized in this setting. This study aimed to define the genomic mechanisms, clonal distribution, and genotype-phenotype relationships of fluoroquinolone resistance in clinical E. coli isolates from Nigeria.</p><p><strong>Methods: </strong>A cross-sectional study of 107 clinical E. coli isolates was conducted. Phenotypic susceptibility to ciprofloxacin and nalidixic acid was determined using VITEK 2 and broth microdilution. Whole-genome sequencing was performed, and analysis included detection of quinolone resistance determining region (QRDR) mutations (gyrA, parC, parE) and plasmid-mediated quinolone resistance (PMQR) genes, multilocus sequence typing (MLST), and phylogenetic analysis. Statistical associations were evaluated using chi-squared tests or Fisher's exact tests.</p><p><strong>Results: </strong>Ciprofloxacin non-susceptibility was high at 86.0%. Resistance was primarily driven by a conserved chromosomal mutation profile; the combination of gyrA S83L, gyrA D87N, and parC S80I was present in 85 isolates and was associated with ciprofloxacin non-susceptibility in all affected isolates in this cohort. Isolates with only gyrA mutations were resistant to nalidixic acid but susceptible to ciprofloxacin, consistent with a stepwise resistance pathway. In this cohort, the triple QRDR signature (gyrA S83L + gyrA D87N/Y + parC S80I) was a perfect positive predictor of ciprofloxacin non-susceptibility (85/85; 100%). The ST131 lineage dominated, accounting for 21.5% of isolates and universally carrying the complete triple QRDR profile; notably, no ST131 isolate carried a PMQR determinant. Plasmid-mediated quinolone resistance (PMQR) genes were detected in 15.0% of isolates but were not independently associated with ciprofloxacin non-susceptibility in this cohort in the absence of concomitant QRDR mutations. Efflux pump genes were ubiquitous and non-predictive. Notably, six isolates, all from urine, were non-susceptible (R/I) despite lacking all known QRDR and PMQR determinants, pointing to uncharacterized mechanisms. In a multivariable logistic regression model that included ST131 status, PMQR carriage, and parE mutation status, ST131 was associated with ciprofloxacin non-susceptibility (adjusted OR 5.96, 95% CI 1.21-29.4, p = 0.028), whereas PMQR carriage was not (adjusted OR 0.94, 95% CI 0.18-4.85, p = 0.94). The triple QRDR signature was not included in this model because it perfectly predicted ciprofloxacin non-susceptibility in this cohort. Resistance patterns varied by clinical source, with the highest burden in bloodstream and wound infections. This stepwise hierarchy from first-step gyrA muta","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Familial lymphoma and genetic predisposition: an updated review.","authors":"Laura Braun, Rossella Graffeo, Kalaruban Kapilan, Harpreet Kaur Mandhair, Manuela Rabaglio, Urban Novak","doi":"10.1186/s12920-026-02411-9","DOIUrl":"10.1186/s12920-026-02411-9","url":null,"abstract":"<p><strong>Background: </strong>Several factors contribute to the development of malignant lymphomas including environmental exposures, bacterial and viral infections, as well as familial and genetic factors.</p><p><strong>Main body: </strong>Numerous somatic variants are involved in lymphomagenesis, and an increasing number of germline variants predisposing patients to lymphoid neoplasm have been identified. Although most lymphomas arise sporadically, epidemiological studies have linked a familial history of lymphomas and other hematological tumors with an increased lymphoma risk. Although rare, familial clustering of malignant lymphoma is well documented, and the constellations suggest inherited risk factors. Recent technological advancements have improved our ability to identify genetic factors associated with lymphoma that overall lead to a better understanding of genetic susceptibility for these entities. In this context, we here provide a comprehensive perspective on lymphoma risk factors to support improved lymphoma risk assessment and testing. A dedicated clinical management could influence future advances in lymphoma therapies and might also prevent severe toxicity and secondary malignancies. However, to date, only few susceptibility genes for malignant lymphomas have been identified. Highly penetrant mutations in known genes cannot account for most of the excess in a polygenic and heterogenic disease such as cancer. High-throughput sequencing identifies pathogenic variants that may constitute most low-penetrance alleles. However, their detection requires many well-characterized cases and controls. In this review, we therefore also include a short discussion on a Swiss cohort where we prospectively collect and samples for genetic data from individuals with a family history of lymphoma. We are convinced that such an approach is more informative and feasible than a population-based project with unselected cases and aim to better inform both genetic counsellors and oncologists.</p><p><strong>Conclusion: </strong>Inherited genetic factors contribute to lymphoma risk in a subset of patients. Improved identification of susceptibility variants, particularly through family-based studies, may enhance risk assessment and inform personalized clinical management.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk mediators implicated in the Stevens-Johnson Syndrome through gene regulatory network analysis.","authors":"Makoto Watanabe, Mayumi Ueta, Hiromi Nishigaki, Katsura Mizushima, Yuji Naito, Shigeru Kinoshita, Chie Sotozono, Jun Takayama","doi":"10.1186/s12920-026-02415-5","DOIUrl":"10.1186/s12920-026-02415-5","url":null,"abstract":"<p><p>Stevens-Johnson syndrome (SJS) is a rare and severe mucocutaneous disorder often triggered by medications or infections. Our previous research identified that four key genes, Ikzf1, Ptger3, Mavs, and Tlr3 are involved in SJS susceptibility and the conjunctival epithelial innate immune response, demonstrating their role in regulating interferon-stimulated genes. However, the interplay among these regulatory factors remains unclear. This study aimed to elucidate the crosstalk mechanisms between the pathways regulated by these four genes in conjunctival epithelial cells. We constructed a comprehensive gene regulatory network using transcriptomic data from murine conjunctival epithelial cells under 16 distinct conditions, including polyI:C stimulation across wild-type, knockout, and transgenic backgrounds for the key genes. A targeted network analysis systematically identified numerous candidate genes mediating the crosstalk between the regulatory pathways initiated by Ikzf1, Ptger3, Mavs, and Tlr3. The identified candidates suggest the involvement of diverse signaling pathways previously unlinked to SJS pathology. Our findings suggest that the pathogenesis of SJS may arise not from the dysfunction of isolated genes but from the disruption of a balance maintained by intricate pathway crosstalk.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and validation of a prognostic SPP1/PLAU signature in HPV-negative oropharyngeal squamous cell carcinoma.","authors":"Gang Jin, Huijun Yang, Juan Du, Lifang Shang, Ningning Shen, Lei Miao, Siying Liu, Zhiqing Yang, Xuzhi Wang, Rong Wei, Wenxia Ma, Yanfeng Chen, Chen Wang","doi":"10.1186/s12920-026-02400-y","DOIUrl":"10.1186/s12920-026-02400-y","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to identify and validate robust prognostic biomarkers for oropharyngeal squamous cell carcinoma (OPSCC), with a specific focus on the high-risk HPV-negative subtype.</p><p><strong>Methods: </strong>Integrated bioinformatics analysis was performed on transcriptomic data from four GEO datasets (n = 418 samples). Differentially expressed genes (DEGs) were identified, and a protein-protein interaction (PPI) network was constructed for the most dysregulated genes. Key modules were analyzed via survival analysis and multivariate Cox regression. The top candidate genes were validated at the protein level using immunohistochemistry (IHC) in an independent cohort of 304 OPSCC patients.</p><p><strong>Results: </strong>A 33-gene module related to extracellular matrix organization showed significant prognostic association. It stratified patients into high- and low-risk groups with markedly different overall survival (HR = 2.71, p < 0.001). From this module, SPP1 and PLAU were identified as independent prognostic factors through multi-step screening. Both genes were significantly overexpressed in tumors (approximately 20-fold and 10-fold, respectively, p < 0.001), with high expression strongly correlated with advanced tumor stage (p < 0.01) and, notably, the HPV-negative subtype (p < 0.001). In survival analysis, high expression of either SPP1 or PLAU was associated with poorer overall survival (SPP1: p < 0.001; PLAU: p < 0.001) and progression-free survival (p < 0.001). IHC validation confirmed high protein expression in 69.7% (SPP1) and 54.8% (PLAU) of cancer tissues. A prognostic nomogram integrating the SPP1/PLAU signature with clinical variables was constructed with strong predictive accuracy (C-index = 0.75).</p><p><strong>Conclusion: </strong>The SPP1/PLAU dual-gene signature is a robust and independent prognostic biomarker for OPSCC, with particular clinical utility for stratifying high-risk HPV-negative patients.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic diversity of the Plasmodium falciparum msp2 gene in children from the Eastern Democratic Republic of Congo: a comparative study of clinical and subclinical infections.","authors":"Moski Morisho Nasibu, Lambert Morisho Mulakwa, Serge Muganda Chirimwami, Charles Bamavu Amisi, Justin Byamungu Ahadi, Rodrigue K Zakitoka, André N H Bulabula, Ali Bulabula","doi":"10.1186/s12920-026-02413-7","DOIUrl":"10.1186/s12920-026-02413-7","url":null,"abstract":"<p><strong>Background: </strong>Plasmodium falciparum is the main cause of malaria-related illness and death in sub-Saharan Africa. Despite control efforts, asymptomatic carriers, particularly children, continue to sustain transmission. Improving surveillance requires a better understanding of the genetic diversity and parasite burden of symptomatic versus asymptomatic infections.</p><p><strong>Objective: </strong>To compare Plasmodium falciparum genotypic profiles and msp2 gene copy numbers in symptomatic and asymptomatic children in Kindu, and assess associations with clinical status.</p><p><strong>Methods: </strong>Children aged 6 months to 12 years were recruited from health centres and schools. DNA extracted from dried blood spots (Chelex^® 100) was analysed by nested PCR to identify msp2 allelic families (FC27, 3D7, multiplicity of infection) and by quantitative PCR to estimate copy number. Statistical tests compared groups and predictors of symptomatic infection.</p><p><strong>Results: </strong>Of the 522 children included, those in the symptomatic group were younger than those in the asymptomatic group (mean age: 5.77 vs. 7.25 years; p < 0.001) and were more frequently male (70%). P. falciparum prevalence was higher among symptomatic children (69.8%). The FC27 allele family and polyclonal infections (higher multiplicity of infection) were strongly associated with symptomatic malaria (aOR = 6.50 and 24.58, respectively; p < 0.01). Gene copy number was higher in symptomatic and polyclonal infections, but was not independently associated with clinical status after multivariable adjustment (aOR = 0.98; p = 0.134). Parasite positivity remained a strong independent predictor of symptomatic disease (aOR = 3.83; p < 0.001).</p><p><strong>Conclusion: </strong>Symptomatic malaria in children is more closely associated with parasite genotype diversity than density. This emphasises the importance of control strategies for molecular surveillance.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of CASQ2 promotes vascular smooth muscle cell phenotypic switching in aortic dissection uncovered by integrated single-cell transcriptomics.","authors":"Kaiyan Chen, Meixiang Wang, Zhiyuan Zhang, Yingquan Chen, Hui Zhu, Ting Yang, Yuan Xia, Maomao Guo, Junchao Li","doi":"10.1186/s12920-026-02410-w","DOIUrl":"10.1186/s12920-026-02410-w","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Aortic dissection (AD) is a life-threatening cardiovascular disease with limited effective therapeutic options. Phenotypic switching of aortic vascular smooth muscle cells (VSMCs) from a contractile to a pathological state is a critical driver of AD progression. However, the molecular regulators governing this transition remain incompletely understood. This study aimed to identify a critical regulator of VSMC phenotypic switching in AD and to investigate its underlying mechanisms and translational relevance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing datasets obtained from the Gene Expression Omnibus (GEO) database were integrated for analysis. To enhance robustness and reduce dataset-specific bias, weighted gene co-expression network analysis (WGCNA) was performed in both aortic aneurysm (AA) and AD cohorts to identify gene modules associated with VSMC function. Overlapping VSMC-related modules were intersected to define candidate genes. Key regulators were further prioritized in AD datasets using LASSO regression and validated by single-cell RNA sequencing (scRNA-seq) pseudotime trajectory analysis to delineate dynamic gene expression during VSMC phenotypic switching. Functional validation was conducted in an angiotensin II (Ang II)-induced experimental AD mouse model with AAV9-mediated CASQ2 overexpression, as well as in primary VSMCs isolated from the abdominal aorta of mice and treated with Ang II in vitro. Aortic morphology, medial calcification, VSMC phenotypic markers, intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; homeostasis, and endoplasmic reticulum (ER) stress signaling were systematically evaluated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;WGCNA identified a conserved gene module comprising 64 genes associated with VSMC phenotypic transition. Integrative LASSO and scRNA-seq analyses prioritized CASQ2 as a key gene with reduced expression in AD VSMCs. Pseudotime analysis revealed progressive downregulation of CASQ2 during osteochondrogenic phenotypic switching. In AngII-induced experimental AD mice, CASQ2 expression was decreased in the aortic media and accompanied by enhanced medial calcification. In vivo, Ang II infusion markedly reduced aortic CASQ2 expression and induced medial dilation and calcification, accompanied by increased mortality. AAV9-mediated CASQ2 overexpression significantly improved survival, attenuated aneurysmal enlargement, reduced vascular calcification and partially restored contractile marker expression. In vitro, Ang II stimulation decreased CASQ2 levels in primary VSMCs, promoted osteochondrogenic marker expression, and induced intracellular Ca²⁺ overload. CASQ2 overexpression restored calcium-release complex components, suppressed cytosolic Ca²⁺ elevation, and markedly reduced ER stress activation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;CASQ2 may represent a VSMC-enriched functional regulator involved in AD-associated phenotypic switching through calci","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kyphoscoliotic Ehlers-Danlos syndrome due to a novel homozygous PLOD1 variant: severe vascular involvement and molecular diagnosis.","authors":"Yan Yu, Yimo Zeng, Yingdi Liu, Yaning Liu, Qingxin Shi, Huimin Zhu, Juan Wen, Desheng Liang, Zhuo Li, Lingqian Wu","doi":"10.1186/s12920-026-02391-w","DOIUrl":"10.1186/s12920-026-02391-w","url":null,"abstract":"<p><strong>Background: </strong>Kyphoscoliotic Ehlers-Danlos syndrome (kEDS, OMIM: #225400) is a rare subtype of Ehlers-Danlos syndrome characterized by joint hypermobility and spinal deformity, with occasional vascular complications. The rarity of vascular phenotypes in kEDS often leads to low clinical suspicion, contributing to delayed diagnosis and poor outcomes.</p><p><strong>Case presentation: </strong>We report a 13-year-old boy who presented with joint laxity, scoliosis, blue sclerae, and pectus excavatum, and who ultimately succumbed to aortic rupture. Initial whole-exome sequencing (WES) and copy number variation (CNV) analysis failed to identify a causative variant, and genes associated with Marfan syndrome were excluded by WES and multiplex ligation-dependent probe amplification (MLPA). Upon re-analysis of the WES data, however, a homozygous deletion spanning exons 15-16 of PLOD1 was detected and subsequently confirmed by quantitative PCR.</p><p><strong>Conclusions: </strong>This case demonstrates that small exon deletions in PLOD1 may not be reliably detected by routine WES/CNV pipelines, leading to diagnostic delay, and underscores the underrecognized vascular risk in kEDS. Clinicians should maintain vigilance for vascular complications in patients with kEDS and consider re-analysis strategies to ensure timely diagnosis and appropriate genetic counseling.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148222952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of genetic variants in TCF7L2, MC4R, AGT and ACE genes with cardiometabolic diseases in Black South Africans.","authors":"Ndonwi Elvis Ngwa, Keren de Buys, Don Makwakiwe Matshazi, Naomi S Levitt, Carl Lombard, Glenda Mary Davison, Tandi Edith Matsha, Andre Pascal Kengne, Sian Megan Joanna Hemmings, Nasheeta Peer","doi":"10.1186/s12920-026-02395-6","DOIUrl":"10.1186/s12920-026-02395-6","url":null,"abstract":"<p><strong>Background: </strong>Our study investigated the association between transcription factor 7-like 2 (TCF7L2-rs7903146), angiotensin convertase enzyme (ACE-rs4646994), angiotensinogen (AGT-rs699), angiotensin II type 1 receptor (AGT1R-rs5186), fat mass and obesity-associated (FTO-rs17817499) and melanocortin 4 receptor (MC4R-rs17782313, rs12970134 and rs229616) single nucleotide polymorphisms (SNPs) with type 2 diabetes (T2D), obesity and hypertension in a Black South African population.</p><p><strong>Methods: </strong>This cross-sectional study involved 560 Black South Africans aged 25 to 74 years. Participant demographic and lifestyle characteristics were self-reported; anthropometry and blood pressures (BP) measured; oral glucose tolerance tests used to diagnose T2D; and SNPs genotyped by polymerase chain reaction. The Benjamini-Hochberg method was used to control for multiple hypothesis testing, using a significance threshold of 0.12.</p><p><strong>Results: </strong>Using the median test, systolic BP was significantly higher in carriers of the G/G genotype of rs229616 within the MC4R gene compared to carriers of the G/A genotype (p = 0.006, p-FDR = 0.030). In the same gene, logistic regression analysis showed that carriers of the minor C/C genotype of the rs17782313 SNP had a significantly higher risk of hypertension (OR = 1.37, p = 0.023, p-FDR = 0.115) in the unadjusted model. However, the significance was attenuated after adjusting for age, gender and BMI (OR = 1.32, p = 0.084, p-FDR = 0.140). Moreover, carriers of the minor T/T genotype of the TCF7L2 rs7903146 SNP had a lower risk of T2D in the crude model (OR = 0.66, p = 0.043, p-FDR = 0.108) and after adjustment for age, gender and BMI (OR = 0.63, p = 0.041, p-FDR = 0.108). These findings remained significant after correction for multiple comparisons.</p><p><strong>Conclusion: </strong>TCF7L2-rs7903146 (C/C genotype) and MC4R-17,782,313 (C/C genotype) SNPs are potential genetic risk factors for T2D and hypertension, respectively, in the Black South African population. Replicating these findings and exploring the role played by these genetic variants in downstream molecular pathways could aid in risk stratification and facilitate personalized approaches to healthcare delivery.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13488011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A founder variant in TANGO2 p.(Leu148Trp) in ten Palestinian families: clinical characterization and haplotype analysis of TANGO2 deficiency disorder.","authors":"Christina Canavati, Motee Ashhab, Grace Rabie, Lina Hreimat, Hanin Shatrit, Lara Kamal, Fouad Zahdeh, Dania Dajani, Osama Atawneh, Mohammed Ali Alsharha, Nadirah Damseh, Bassam Abu-Libdeh, Imad Dweikat, Nader Handal, Moien Kanaan","doi":"10.1186/s12920-026-02407-5","DOIUrl":"10.1186/s12920-026-02407-5","url":null,"abstract":"<p><strong>Background: </strong>TANGO2 deficiency disorder (TDD) is a rare autosomal recessive condition characterized by recurrent metabolic crises, rhabdomyolysis, encephalopathy, seizures, intellectual disability, and life-threatening cardiac arrhythmias.</p><p><strong>Methods: </strong>Here, we describe 16 affected individuals from 10 consanguineous Palestinian families harboring a shared homozygous missense variant in TANGO2 (NM_152906.7:c.443T > G; NP_690870.3:p.(Leu148Trp)). Exome sequencing identified the variant in three probands and targeted Sanger sequencing confirmed segregation in all remaining families. The variant is absent from population databases and is predicted to be deleterious by multiple in silico tools. Microsatellite marker analysis was performed using five short tandem repeat (STR) markers spanning the TANGO2 locus.</p><p><strong>Results: </strong>Clinical presentation was heterogeneous, including developmental delay, recurrent encephalopathy, rhabdomyolysis, seizures, and cardiac involvement. Microsatellite marker analysis revealed a conserved ancestral haplotype flanking the TANGO2 locus in all genotyped affected individuals, supporting a founder effect in this population. Supportive management including coenzyme Q10 and B-complex vitamins (B-100) was commonly used; consistent with prior reports, some families described reduced frequency and/or severity of spells following supplementation.</p><p><strong>Conclusions: </strong>These findings provide strong clinical, genetic, and haplotype evidence supporting reclassification of the TANGO2 p.(Leu148Trp) variant as likely pathogenic and highlight the importance of early molecular diagnosis and targeted screening strategies in high-consanguinity populations.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: apolipoprotein D downregulation in OSCC: multi-database validation and clinical significance.","authors":"Shuting Wang, Jun Zhao, Rui Bai, Jianbo Ou, Chan Tang, Jiayi Hang, Xiaolin Nong","doi":"10.1186/s12920-026-02404-8","DOIUrl":"10.1186/s12920-026-02404-8","url":null,"abstract":"","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"19 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13244988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}