BMC Medical Genomics[JOURNAL]
Sun
200 papers
Associations of the gut microbiome and cardiometabolic risk in adolescence: the HOME study.
Arzu JL, Fleury ES, Cecil KM … +6 more , Chen A, Lanphear BP, Yolton K, Buckley JP, Braun JM, Laue HE
BMC Med Genomics · 2026 Apr · PMID 41928235 · Full text
BACKGROUND: Alterations to the gut microbiome have been linked to cardiometabolic disease, like type 2 diabetes and hypertension, in adults, but few studies have investigated these associations in adolescents. We examine...
BACKGROUND: Alterations to the gut microbiome have been linked to cardiometabolic disease, like type 2 diabetes and hypertension, in adults, but few studies have investigated these associations in adolescents. We examined the relation between the gut microbiome and cardiometabolic risk in adolescence and determined whether sex and race/ethnicity modified these associations. METHODS: In 144 adolescents (age range: 11–14 years) from the Health Outcomes and Measures of the Environment (HOME) Study, we quantified gut microbiome alpha diversity using the Shannon index and species’ relative abundances (i.e., centered log-ratio normalized abundances) in stool DNA that underwent metagenomic sequencing. We assessed adolescent cardiometabolic risk using a cardiometabolic risk summary score, its individual components (i.e., visceral fat, leptin to adiponectin ratio, HOMA-IR, triglyceride to high-density lipoprotein cholesterol ratio, and systolic blood pressure), as well as total cholesterol and hemoglobin A1c. We used linear regression models to estimate covariate-adjusted cross-sectional associations of the Shannon diversity index and species’ relative abundances with cardiometabolic risk, and examine differences in these associations by sex and race/ethnicity. At the species level, the false discovery rate (FDR) correction, with q-value < 0.20, was considered statistically significant. RESULTS: Among all adolescents, a higher Shannon diversity index was associated with lower systolic blood pressure [β: -0.18 (95% CI: -0.35, -0.01)] in covariate-adjusted models. However, the associations of the Shannon diversity index with cardiometabolic risk did not differ significantly by sex or race/ethnicity. Although associations of the relative abundances of species, prevalent in at least 10% of samples, with cardiometabolic risk were not statistically significant tamong all adolescents after correcting for multiple comparisons (qFDR ≥ 0.20), sex modified the association of the relative abundance of Ruminococcus lactaris with HOMA-IR (qinteraction = 0.151), with positive association among females [β: 2.05 (95% CI: 0.93, 3.17), q = 0.155] and suggestive negative association among males [β: -0.84 (95% CI: -1.59, -0.09), q = 0.983]. Associations of the relative abundances of Streptococcus parasanguinis (qinteraction = 0.097), Enterocloster SGB14313 (qinteraction = 0.097), and Alistipes ihumii (qinteraction = 0.097) with total cholesterol also differed between female and male adolescents. We observed differences between adolescents of non-Hispanic black and non-Hispanic white race/ethnicity in the association of the relative abundance of Lachnospira pectinoschiza (qinteraction = 0.028) with total cholesterol. CONCLUSIONS: Our findings suggest that the gut microbiome is associated with cardiometabolic risk in adolescence in a sex-specific manner, and may differ by race and ethnicity.
Palmitoylation remodeling dictates HCC heterogeneity: implications for subtype-specific prognostication and targeting the YAP-RhoA axis.
Xu B, Dai J, Chen Z
BMC Med Genomics · 2026 Apr · PMID 41923085 · Full text
Palmitoylation, a critical post-translational modification mechanism, plays a pivotal role in hepatocellular carcinoma (HCC) tumorigenesis and progression. While multiple palmitoylated proteins have been reported to regu...
Palmitoylation, a critical post-translational modification mechanism, plays a pivotal role in hepatocellular carcinoma (HCC) tumorigenesis and progression. While multiple palmitoylated proteins have been reported to regulate HCC development, systematic characterization of palmitoylation-associated gene signatures and molecular subtyping based on these regulators remains unexplored. Integrated analysis of transcriptomic profiles enabled stratification of HCC into two distinct palmitoylation-associated molecular subtypes through unsupervised consensus clustering. These subtypes exhibited significant heterogeneity in clinical outcomes, tumor microenvironment features, and therapeutic vulnerabilities. A palmitoylation-related prognostic signature was constructed via LASSO-Cox regression. PAL1 showed a marked association with activated cell cycle programs, epithelial-mesenchymal transition (EMT), and WNT/β-catenin signaling. This subtype also correlated with elevated tumor mutation burden (TMB) and poorer patient prognosis. Conversely, PAL2 was closely associated with the expression of differentiation markers and upregulated lipid metabolic processes. Significantly, pronounced molecular divergence characterized the two PAL subtypes. Additionally, ARHGEF3 was critically identified as a key discriminator between the PAL subtypes, and its expression level was significantly correlated with patient prognosis in HCC. ARHGEF3 was upregulated in HCC and demonstrated functional potential to drive tumor cell proliferation and migration, potentially mediated by the YAP-RhoA signaling cascade. Collectively, this study identifies novel molecular biomarkers and thereby establishes a robust framework for clinical translation.
The association of periodontitis with telomere length: a meta-analysis.
Sun Q, Xiao J, Huo J
BMC Med Genomics · 2026 Apr · PMID 41923055 · Full text
BACKGROUND: Telomere length (TL) is a biomarker of biological aging and has been linked to various health outcomes; however, its relationship with periodontitis remains inconsistent. This meta-analysis aimed to evaluate...
BACKGROUND: Telomere length (TL) is a biomarker of biological aging and has been linked to various health outcomes; however, its relationship with periodontitis remains inconsistent. This meta-analysis aimed to evaluate the association between periodontitis and TL. METHODS: PubMed, Scopus, Medline, and Embase databases were searched for relevant studies published until August 2025. The differences in mean TL between those with and without periodontitis were measured using standardized mean difference (SMD) with 95% confidence intervals (CIs), while standardized beta coefficients (β) and their 95% CIs were applied to assess the strength of the association using a random effects model. RESULTS: Ten observational studies including 22,625 participants were analyzed. The overall results indicated no significant difference in mean TL between individuals with and without periodontitis (SMD = -0.03, 95% CI = -0.09 to 0.03). Additionally, no significant association was observed between periodontitis and TL (β = -0.001, 95% CI = -0.01 to 0.01). Subgroup analysis revealed that patients under 50 years old (SMD = -0.25, 95% CI = -0.41 to -0.09) and Asian patients (SMD = -0.44, 95% CI = -0.82 to -0.06) had significantly shorter TL compared to those without periodontitis. Additionally, periodontitis was significantly inversely associated with TL in these groups (age < 50: β = -0.07, 95% CI = -0.11 to -0.03; Asians: β = -0.20, 95% CI = -0.38 to -0.03). CONCLUSION: Periodontitis may be linked to shorter TL, indicating that TL could potentially serve as a biomarker for periodontal health.
A novel homozygous splicing variant in FREM1 expands the phenotypic spectrum of BNAR syndrome: functional validation and successful PGT-M.
Yan L, Liu Y, Zhang Y … +5 more , Han C, Cao J, Zou J, Luo H, Li H
BMC Med Genomics · 2026 Apr · PMID 41923049 · Full text
BACKGROUND: Bifid nose with or without anorectal and renal anomalies (BNAR) is a rare autosomal recessive genetic congenital disorder characterized by bifid nose and renal agenesis, with or without anorectal malformation...
BACKGROUND: Bifid nose with or without anorectal and renal anomalies (BNAR) is a rare autosomal recessive genetic congenital disorder characterized by bifid nose and renal agenesis, with or without anorectal malformations. Our research identified the genetic factors associated with BNAR in a Chinese pedigree. METHODS: Muscle tissue specimens from the fetus and peripheral blood specimens from the parents were collected, and genomic DNA was extracted for whole-exome sequencing. Sanger sequencing was used to verify the emergence of variants in the pedigree. Minigene assays and structural modeling were performed to confirm the influence of intronic variants on mRNA splicing. RESULTS: We identified a homozygous splicing variant, c.3274 + 4 A > G, in the FREM1 gene in the fetus. Sanger sequencing revealed that the parents were heterozygous. In vitro and in intro minigene assays revealed exon 18 skipping, causing a nonframeshift, 62 amino acid deletion in FREM1. Structural predictions indicate the deletion severely disrupts the FREM1 CSPG6 domain, replacing its stable interwoven β-sheet architecture with a single β-sheet and an aberrant α-helix. This profound conformational shift likely abolishes the interaction interfaces required for FRAS1/FREM multiprotein complex assembly, impairing its overall function. Based on these findings, the variant was categorized as likely pathogenic according to the American College of Medical Genetics and Genomics guidelines. Accordingly, after being informed about the hazards of the pathogenic variant, the couple selected preimplantation genetic tests for monogenic disorders (PGT-M) and had a healthy baby. CONCLUSION: This study presents a Chinese fetus with FREM1-related pathology. Moreover, this study extends the phenotypic spectrum of BNAR, while laying a foundation for PGT-M.
A novel MYO6 variant identified in a Chinese family with autosomal dominant non-syndromic hearing loss.
Wang J, Zhu QW, Cui AM … +1 more , Lou HQ
BMC Med Genomics · 2026 Apr · PMID 41923037 · Full text
BACKGROUND: Hereditary hearing loss (HL) is a highly heterogeneous disorder that follows various inheritance patterns. Variants of MYO6 gene in DFNA22 are characterised by progressive post-lingual sensorineural HL of var...
BACKGROUND: Hereditary hearing loss (HL) is a highly heterogeneous disorder that follows various inheritance patterns. Variants of MYO6 gene in DFNA22 are characterised by progressive post-lingual sensorineural HL of varying severity. PATIENTS AND METHODS: Five-generation Chinese family with autosomal dominant non-syndromic hearing loss (ADNSHL) was enrolled in this study. Whole-exome sequencing (WES) was performed on the proband and her father to screen for causal variants in the genome, whereas intrafamilial co-segregation of the candidate variants in family members was verified using Sanger sequencing. Furthermore, protein modelling and stability analyses were performed to assess the potential pathogenicity of the candidate mutations. RESULTS: A previously unreported heterozygous missense variant (NM_004999.4:c.2063 A > G, p.Gln688Arg) in exon 20 of MYO6 using WES and was found to co-segregated with the disease in this family. Molecular dynamics simulations predict that the glutamic acid-to-arginine change in p.(Gln688Arg) alters the normal function, most likely through the altered intermolecular forces of this amino acid with the three nearby polar residues. The structural changes caused by this mutation could potentially affect the myosin ATPase cycle. CONCLUSIONS: We report a novel likely pathogenic missense (c.2063 A > G) variant within of MYO6 in patients with DFNA22. Our findings expand the variant spectrum of MYO6 and ADNSHL in Chinese individuals, which will facilitate early clinical genetic diagnosis and accurate genetic counselling of patients.
Long-read sequencing identifies complex structural variants in DMD patients.
Xie Y, Bao L, Yu X … +1 more , Liu Y
BMC Med Genomics · 2026 Mar · PMID 41906116 · Full text
BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by mutations in the DMD gene. Reports of DMD resulting from complex structural variants involving the DMD gene are rare, partly because such va...
BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by mutations in the DMD gene. Reports of DMD resulting from complex structural variants involving the DMD gene are rare, partly because such variants are often undetectable by standard diagnostic approaches such as multiplex ligation-dependent probe amplification (MLPA) and short-read whole-exome sequencing (WES). CASE PRESENTATION: Using long-read sequencing, we identified two unrelated pedigrees with complex structural rearrangements affecting the DMD locus. Case 1 carried an inversion encompassing exon 2 of DMD. Case 2 harbored a large-scale inversion of the DMD gene accompanied by two segmental duplications arising as a direct consequence of the inversion; the entire complex allele was maternally inherited. In both instances, simple tandem repeats were present at most of the breakpoints. CONCLUSIONS: Our findings demonstrate that long-read sequencing is a powerful tool for resolving complex structural variants. The simple tandem repeats identified at the inversion breakpoints in DMD patients enhance our understanding of the mutational mechanisms underlying structural variation, which in turn aids in developing potential therapeutic strategies.
A case report of a family with MYH9 gene mutation-related disease in an ethnic minority group and literature review.
Yan X, Li Z, Huang S … +4 more , Yang X, Chang M, Cheng Z, Zhou LT
BMC Med Genomics · 2026 Mar · PMID 41904450 · Full text
BACKGROUND: May-Hegglin anomaly, a rare autosomal dominant disorder caused by MYH9 mutations, is characterized by the classic "triad" of thrombocytopenia, giant platelets, and granulocyte cytoplasmic inclusion bodies; so...
BACKGROUND: May-Hegglin anomaly, a rare autosomal dominant disorder caused by MYH9 mutations, is characterized by the classic "triad" of thrombocytopenia, giant platelets, and granulocyte cytoplasmic inclusion bodies; some patients also present non-hematological symptoms. RESULTS: We reported a family of MYH9-related disease. The proband had microscopic hematuria, proteinuria, and thrombocytopenia on physical examination; blood smear re-examination showed giant platelets and Döhle-like bodies. His medical history included childhood epistaxis; his father had unexplained thrombocytopenia/proteinuria, and his younger brother had epistaxis/purpura/thrombocytopenia. Whole-exome sequencing (validated by Sanger sequencing) confirmed the diagnosis. CONCLUSIONS: Diagnosis of MYH9-related diseases depends on combined laboratory morphology and molecular biology. Routine blood tests and smear microscopy (identifying abnormal giant platelets/Döhle-like bodies) provide initial screening clues, while gene sequencing enables accurate diagnosis and pathogenesis clarification, forming a complete screening-to-confirmation diagnostic pathway.
A novel maternally inherited CDKN1C variant in a familial beckwith-wiedemann syndrome case: expanding the genotype-phenotype spectrum.
Wu S, Zhang Y, Zhang H … +2 more , Yan X, Pi Y
BMC Med Genomics · 2026 Mar · PMID 41888894 · Full text
BACKGROUND: Cyclin-dependent kinase inhibitor 1 C (CDKN1C), encoding the p57KIP2 protein, serves as a critical negative regulator of cellular proliferation. Loss-of-function mutations in CDKN1C are responsible for 5–8% o...
BACKGROUND: Cyclin-dependent kinase inhibitor 1 C (CDKN1C), encoding the p57KIP2 protein, serves as a critical negative regulator of cellular proliferation. Loss-of-function mutations in CDKN1C are responsible for 5–8% of sporadic and 40% of familial Beckwith-Wiedemann syndrome (BWS) cases, with 133 variants catalogued in the Human Gene Mutation Database (HGMD). We herein report a novel CDKN1C variant in a familial BWS case. A female neonate delivered preterm via cesarean section for severe preeclampsia manifested large for gestational age, macroglossia, omphalocele, and nevus flammeus. Immediate postnatal repair of the omphalocele was conducted. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) analysis of genomic DNA from peripheral blood demonstrated normal methylation at the 11p15.5 imprinting control region without copy number variations. Whole-exome sequencing (WES) showed no pathogenic variants, whereas whole-genome sequencing (WGS) detected a novel maternally inherited heterozygous frameshift variant in CDKN1C (NM_000076.2: c.617_635dup, p.Ala213GlyfsTer34). Longitudinal follow-up to age 4.5 years documented persistent postnatal overgrowth, with weight consistently tracking above the 97th percentile ( > + 2 SD). Motor, language, and cognitive development had gradually improved, progressing from mild delay to normal status. A transient leg length difference was initially noted but resolved on follow-up examination. The tumor marker alpha-fetoprotein (AFP) had normalized, and no tumors were detected during monitoring. CONCLUSION: This case reinforces the critical link between CDKN1C loss-of-function variants and abdominal wall defects. Our findings underscore the necessity of CDKN1C sequencing in Beckwith-Wiedemann spectrum (BWSp) diagnostics, particularly for fetuses presenting with omphalocele and negative 11p15 epigenetic testing. The identification of the novel NM_000076.2: c.617_635dup variant expands the genotype-phenotype landscape of BWS, facilitating more precise genetic counseling and subtype-specific management.
Pharmacogenomic study of the effects of saxagliptin on glucose control and hypoglycemic events.
Pilon MO, de Denus S, Asselin G … +11 more , Legault MA, Ngongang Kwandjang HB, Barhdadi A, Lemieux Perreault LP, Valois D, Mongrain I, Haefliger C, Paul DS, Pearson ER, Tardif JC, Dubé MP
BMC Med Genomics · 2026 Mar · PMID 41882721 · Full text
BACKGROUND: Saxagliptin is a DPP-4 inhibitor widely used to manage type 2 diabetes, though genetic contributors to variability in response remain unclear. This study aimed to identify genetic variants associated with the...
BACKGROUND: Saxagliptin is a DPP-4 inhibitor widely used to manage type 2 diabetes, though genetic contributors to variability in response remain unclear. This study aimed to identify genetic variants associated with the efficacy and safety of saxagliptin using genome-wide association studies (GWAS) with data from randomized controlled trials. METHODS: GWAS were conducted on glycated hemoglobin (HbA1c) levels and hypoglycemic events in saxagliptin-treated individuals from 12 phase II or III clinical trials. Additional exploratory traits included fasting glucose, weight, body mass index, systolic and diastolic blood pressure, heartbeat, and renal function. Primary analyses focused on participants of European ancestry, followed by analyses in the overall multi-ancestry cohort. Linear mixed models for continuous traits and Cox proportional hazards models for time-to-event analyses were used, including gene-by-sex and gene-by-treatment interactions. We also performed a transcriptome-wide association study (TWAS) to identify genes whose predicted expression is associated with the response to saxagliptin using the S-PrediXcan framework. RESULTS: Among 1 016 European and 1 826 multi-ancestry saxagliptin-treated participants, no genome-wide significant associations were observed. Suggestive associations included rs2168426:T > C near UBE2E1 for HbA1c (p = 1.0 × 10⁻⁷) and rs138558907:C > T near CCSER2 for hypoglycemia (p = 6.1 × 10⁻⁸). Treatment interaction analyses showed a stronger rs2168426 effect on HbA1c among saxagliptin users compared with non-users (pint = 9.2 × 10⁻³). The TWAS revealed three genes that significantly associated with HbA1c in human tissues: OGFOD3 in aorta (p = 8.3 × 10⁻⁷), TBC1D3D in coronary artery (p = 3.3 × 10⁻⁶), and TYSND1 in amygdala (p = 3.9 × 10⁻⁶). In the multi-ancestry cohort, KDM7A in whole blood was significantly associated with HbA1c (p = 3.6 × 10⁻⁶). CONCLUSION: Larger, diverse studies are needed to identify pharmacogenomic determinants of responses to saxagliptin.
Pathogenomics of multidrug-resistant Escherichia coli from bloodstream infections in South Africa.
Hetsa BA, Yeboah EEA, Ismail A … +2 more , Essack SY, Amoako DG
BMC Med Genomics · 2026 Mar · PMID 41877132 · Full text
BACKGROUND: Escherichia coli (E. coli) is a leading cause of bloodstream infections (BSIs) globally, with multidrug-resistant (MDR) strains complicating treatment outcomes. In South Africa, genomic data on such isolates...
BACKGROUND: Escherichia coli (E. coli) is a leading cause of bloodstream infections (BSIs) globally, with multidrug-resistant (MDR) strains complicating treatment outcomes. In South Africa, genomic data on such isolates remain scarce. To elucidate the genomic landscape of E. coli isolates from bloodstream infections (BSIs) collected over a one-year period in the uMgungundlovu District, South Africa, with a focus on the resistance and virulence genes, mobile genetic elements (MGEs), genetic synteny, sequence types (STs), and phylogenomic context. METHODS: Twenty-five non-duplicate E. coli isolates were recovered from blood cultures and subjected to antimicrobial susceptibility testing. All twelve MDR isolates underwent whole-genome sequencing and bioinformatic analysis. RESULTS: The MDR isolates comprised six distinct STs, notably high-risk international lineages ST131 (33.3%) and ST69 (25.0%), spanning five phylogroups, predominantly B2 and D. Eight O: H serotypes were identified, with O25:H4 and O45:H16 being most frequent. CH-typing revealed dominant CH types CH40-30 (ST131) and CH35-27 (ST69) and fimH alleles such as fimH30 and fimH27. The isolates encoded β-lactamases, including blaCTX-M-15, blaTEM-1B and blaOXA-1, frequently co-located with MGEs. Notably, blaCTX-M-15 was chromosomally integrated within a Tn3–ISEcp1 transposon unit, while blaTEM-1B and blaOXA-1 were associated with diverse plasmid-associated syntenic architectures flanked by IS1, IS91, or integron-associated regions. Other antibiotic resistance genes were detected, conferring resistance to aminoglycosides (aph(3’)-Ia, aac(3)-IIa, aac(3)-IIe, aadA1, aadA2), sulfonamides (sul1, sul2) and trimethoprim (dfrA variants). A diverse array of virulence genes was identified, associated with adhesion, iron acquisition, serum resistance, and toxin production. Phylogenomic clustering revealed close relationships between local ST131/ST69 isolates and counterparts across Africa. CONCLUSIONS: The study identifies diverse MDR E. coli clones circulating in bloodstream infections, notably high-risk lineages ST131, ST69 and ST10, with complex resistance and virulence gene arsenals facilitated by MGEs. These insights reinforce the imperative for genomic surveillance to guide infection control and antibiotic stewardship in high-burden settings.
The genetic landscape of breast cancer in young women from Morocco: implications for diagnosis and treatment.
El Hejjioui B, Bouramtane A, Bouguenouch L … +5 more , Elmakhzen B, Ahakoud M, Melhouf MA, Ouldim K, Bennis S
BMC Med Genomics · 2026 Mar · PMID 41851691 · Full text
Mortality rates from breast cancer in young women have fallen considerably in high-income countries but continue to rise in low-income countries such as Morocco. Young women with breast cancer face unique challenges due...
Mortality rates from breast cancer in young women have fallen considerably in high-income countries but continue to rise in low-income countries such as Morocco. Young women with breast cancer face unique challenges due to the aggressive nature of the disease, the presence of aggressive subtypes (e.g., triple-negative, HER2-positive, and luminal B), and limited access to timely diagnosis and treatment. In addition, genetic factors play crucial roles in patient prognosis and response to treatment. The molecular landscape of breast cancer in young women has important implications for personalized medicine, such as the use of targeted therapies, namely poly (ADP-ribose) polymerase (PARP) inhibitors, which are particularly effective in patients with BRCA gene mutations. However, research into the genetic landscape of breast cancer in young women from low-income regions is limited, and the potential of personalized medicine to improve outcomes remains underexplored.This study aims to analyze the genetic landscape of breast cancer in young Moroccan women, with a focus on genetic alterations beyond the BRCA1 and BRCA2 genes. By expanding the panel of genes, we hope to identify other genetic variants that may influence the diagnosis, treatment, and follow-up of this high-risk population.Methods A retrospective study was conducted on 60 young women who were diagnosed with breast cancer between 2019 and 2024 at Hassan II University Hospital, Fez, Morocco. Genetic analysis was performed via next-generation sequencing (NGS) technology, specifically the Ion S5 sequencer and a custom-designed gene panel targeting 28 key genes associated with breast cancer and hereditary cancer syndromes.For statistical analysis, descriptive statistics were calculated for clinical variables (e.g., age, grades, molecular subtypes, genetic mutations). The correlation between genetic mutations and clinical outcomes was assessed using chi-square tests. All statistical analyses were performed using SPSS software. A significant level of p < 0.05 was used for all tests.Results The cohort had a mean age of 34.6 years, with 36.7% reporting a family history of cancer. DNA sequencing of the 60 patients yielded 15 pathogenic variants and 3 likely pathogenic variants; the genes involved being BRCA1, BRCA2, and ATM for the pathogenic variants, whereas for the likely pathogenic variants, the genes involved were MUTYH and APC, which suggests the presence of other potential genetic risk factors other than the BRCA1 and BRCA2 genes. Furthermore, the BRCA1 gene was mutated in 45% of patients with triple-negative breast cancer, highlighting the important role of genetic testing in identifying high-risk patients, which should greatly improve the management and treatment of the disease.Conclusion This study highlights the importance of genetic testing for personalized treatment of young breast cancer patients. Firstly, these results will help us to improve outcomes for young women with aggressive subtypes in low-income countries through the adaptation of targeted therapies such as PARP inhibitors. Secondly, this study will help us to identify at-risk family members, so that we can detect breast cancer at an early stage and adapt care accordingly. And finally, this study has allowed us to identify genes of interest other than the two BRCA1 and BRCA2 genes, demonstrating the diversity in this population.
From gene to heart: the impact of a novel SGCD variant in familial dilated cardiomyopathy.
Kalayinia S, Poopak A, Soveizi M … +1 more , Maleki M
BMC Med Genomics · 2026 Mar · PMID 41840602 · Full text
BACKGROUND: Dilated cardiomyopathy (DCM) is a leading cause of heart failure, often resulting in reduced ejection fraction and progressive cardiac dysfunction. Although up to half of idiopathic DCM can be linked to genet...
BACKGROUND: Dilated cardiomyopathy (DCM) is a leading cause of heart failure, often resulting in reduced ejection fraction and progressive cardiac dysfunction. Although up to half of idiopathic DCM can be linked to genetic variants, many familial cases still lack a definitive molecular diagnosis. Sarcoglycan delta (SGCD) encodes a crucial component of the dystrophin-glycoprotein complex, and variants in this gene have been implicated in both muscular dystrophies and cardiomyopathies. METHODS: We evaluated a three-year-old girl presenting with a confirmed diagnosis of DCM. Clinical assessments included echocardiography and cardiac magnetic resonance imaging (CMR), revealing moderate-to-severe systolic and diastolic dysfunction. Whole exome sequencing (WES) was performed to investigate potential causative variants. In silico analysis and Sanger sequencing were used to confirm and characterize any identified alteration in the proband and her parents. RESULTS: WES identified a novel heterozygous SGCD variant, NM_000337.6(SGCD): c.647 A > T, p.(Asn216Ile), located in exon 8. Sanger sequencing confirmed this variant’s presence in the proband and her father, suggesting a familial inheritance pattern. In silico predictive tools supported a likely deleterious effect of the variant,, with functional analysis indicating possible disruption of δ-Sarcoglycan’s structure. This variant was absent in public variant databases, underscoring its rarity. Comparative evaluation of known SGCD variants further highlighted exon 8 as a possible mutational hotspot in DCM. CONCLUSION: These findings expand the variant spectrum of SGCD and reinforce its role in familial DCM. Genetic screening for SGCD variants in individuals with idiopathic or familial cardiomyopathy can improve early diagnosis, guide targeted interventions, and inform genetic counseling. Our results underscore the clinical importance of integrating molecular diagnostics to enhance personalized management of DCM.
Unraveling the temporal dynamics of radiation-induced lung injury: a multi-omics integration of transcriptomic, proteomic, and metabolic reprogramming.
Wu D, Tang F, Zhang Y … +5 more , Zhang X, Peng Y, Hou Y, Yang Z, Xu Z
BMC Med Genomics · 2026 Mar · PMID 41814364 · Full text
Radiation-induced lung injury (RILI) arises from the unavoidable exposure of normal lung tissue during radiotherapy for thoracic malignancies. It remains a dose-limiting complication in thoracic radiotherapy, critically...
Radiation-induced lung injury (RILI) arises from the unavoidable exposure of normal lung tissue during radiotherapy for thoracic malignancies. It remains a dose-limiting complication in thoracic radiotherapy, critically impacting treatment efficacy and long-term patient survival. Despite its clinical significance, the dynamic molecular reprogramming underlying RILI progression remains poorly characterized. Utilizing a C57BL/6J thoracic irradiation mouse model validated by histopathological analysis, we implemented an integrative tri-omics approach (RNA-seq, LC-MS/MS proteomics, and UHPLC-QTOF metabolomics) to systematically map the temporal evolution of RILI at critical phases: acute inflammation, transitional, and fibrotic. The three periods correspond to 4 weeks, 8 weeks, and 16 weeks after the mice received 16 Gy of electron beam irradiation to the thoracic region. Combined analysis using complete-linkage hierarchical clustering revealed co-expression modules, and Ces2e was identified as a pivotal node exhibiting sustained upregulation at both transcriptional and translational levels during early pathogenesis. Functional enrichment revealed time-dependent activation of xenobiotic metabolism and extracellular matrix (ECM)-receptor interaction pathways, with Ces2e overexpression correlating with macrophage polarization and lipid peroxidation accumulation. This temporal multi-omics atlas not only deciphers stage-specific molecular signatures of RILI but also nominates Ces2e as a candidate early-stage molecular marker.
Cellular senescence in gastric cancer: a novel prognostic stratification and immune predictor.
Wei CZ, Li YT, Lin ZH … +6 more , Lin FZ, Chen XJ, Nie RC, Chen GM, Xue ZC, Zheng ZQ
BMC Med Genomics · 2026 Mar · PMID 41808162 · Full text
Cellular senescence, a state of permanent arrest of the cell cycle in response to various damage, exerts dual impact on tumor initiation and progression and has emerged as a promising therapeutic target. However, an appl...
Cellular senescence, a state of permanent arrest of the cell cycle in response to various damage, exerts dual impact on tumor initiation and progression and has emerged as a promising therapeutic target. However, an applicable tool to quantify senescence remains exclusive. In this study, we investigated the role of senescence in gastric cancer (GC) progression through the analysis of TCGA-STAD cohort. According to senescence-associated gene (SAG) expression signatures, TCGA-STAD was divided into distinct senescence clusters. Cluster B with elevated expression of SAGs was associated with a poorer prognosis and a tumor microenvironment that was more conducive for tumor growth. Based on prognosis-associated differentially expressed genes (DEGs) between senescence clusters, we constructed cellular senescence score system (SSS) to quantify senescence of GC. SSS could serve as an independent prognostic factor and, notably, has the potential to identify patients who may benefit from immunotherapy. This indicates the strong potential of SSS as a biomarker for predicting immunotherapeutic response. In conclusion, SSS provides a reliable tool for prognosis prediction and treatment strategies for GC patients.
Shared molecular signatures between atrial fibrillation and chronic obstructive pulmonary disease: an integrated bioinformatic analysis with experimental validation.
Zhou W, Tang Q, Chen D … +9 more , Chen J, Shi L, Luo F, Yan F, Mao Y, Lu H, Zhou X, Chen Z, Li W
BMC Med Genomics · 2026 Mar · PMID 41808159 · Full text
BACKGROUND: Atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) are highly prevalent conditions that significantly impact patient outcomes. While mounting evidence suggests a strong epidemiological...
BACKGROUND: Atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) are highly prevalent conditions that significantly impact patient outcomes. While mounting evidence suggests a strong epidemiological and clinical association between AF and COPD, the molecular basis underlying their frequent co-occurrence remains incompletely characterized. Rather than inferring direct disease-specific mechanistic links, this study aimed to identify shared systemic inflammatory and immune-related transcriptional signatures that are detectable across different tissues in AF and COPD. RESULTS: A total of 208 DEGs were found to be shared between AF and COPD. Functional enrichment analyses indicated that these genes were predominantly associated with inflammatory, immune, and extracellular matrix–related biological processes, including the NOD-like receptor, Influenza A, Phospholipase D, and ECM-receptor interaction pathways. PPI network analysis and external dataset verification highlighted CASP1, CXCR2, and IFIT5 as reproducibly upregulated genes across independent AF and COPD transcriptomic datasets. Their elevated expression was further observed in AF, COPD, and comorbid samples in exploratory validation experiments. No single TF or miRNA was found to simultaneously regulate all three genes, suggesting heterogeneous and context-dependent regulatory patterns rather than a unified regulatory axis. Drug–gene association analysis identified estradiol and methyl methanesulfonate as compounds computationally linked to the shared gene set, without implying biological efficacy or therapeutic applicability. CONCLUSION: This study delineates shared inflammatory and immune-related transcriptional signatures observed across AF and COPD datasets, highlighting common pathways and candidate genes that may reflect systemic inflammatory states. These findings are hypothesis-generating and primarily reflect shared systemic inflammatory and immune responses rather than disease-specific causal mechanisms, providing a bioinformatic framework for future mechanistic and clinical investigations.
Apolipoprotein D downregulation in OSCC: multi-database validation and clinical significance.
Wang S, Zhao J, Bai R … +4 more , Ou J, Tang C, Hang J, Nong X
BMC Med Genomics · 2026 Mar · PMID 41808079 · Full text
BACKGROUND: Apolipoprotein D (APOD), a member of the lipocalin superfamily, plays a pivotal role in apoptosis, cancer, immune responses, and neural injury repair. Its association with various cancer types has been well-d...
BACKGROUND: Apolipoprotein D (APOD), a member of the lipocalin superfamily, plays a pivotal role in apoptosis, cancer, immune responses, and neural injury repair. Its association with various cancer types has been well-documented, but its expression and clinical implications in oral squamous cell carcinoma (OSCC) remain underexplored. Our study aims to investigate the expression and clinical significance of APOD in OSCC. METHODS: A comprehensive analysis of APOD mRNA and protein expression in OSCC was conducted using multi-omics data from TCGA, GEO, and CPTAC databases. The findings were validated through qRT-PCR and immunohistochemistry (IHC) on OSCC tissue samples. Diagnostic and prognostic potential of APOD was assessed using summary receiver operating characteristic (sROC) curves and Kaplan-Meier survival analysis. Multivariate Cox regression analysis was performed to adjust for confounding factors and identify independent prognostic markers for survival. Gene set enrichment analysis (GSEA) was used to explore the signaling pathways associated with APOD and their biological relevance. Ethical approval for research involving human subjects was obtained from an ethics committee. RESULTS: Analysis of public databases revealed significant downregulation of both APOD mRNA and protein in OSCC tissues compared to normal mucosal controls. Results from clinical samples corroborated these findings. The sROC analysis indicated that APOD may serve as a promising diagnostic biomarker for OSCC. Multivariate Cox regression analysis identified pathological T stage as an independent prognostic factor, independent of clinical T stage and lymphovascular invasion, while APOD, although associated with prognosis, was not a robust predictor. GSEA highlighted a strong positive correlation between APOD expression and key components of Type I interferon signaling (JAK1, TYK2, STAT2), suggesting that APOD downregulation may contribute to OSCC progression by inhibiting the Type I interferon-JAK-STAT pathway. CONCLUSION: APOD expression is significantly reduced in OSCC, demonstrating potential as a diagnostic and prognostic biomarker. Its downregulation may facilitate disease progression through disruption of the Type I interferon-mediated JAK-STAT signaling pathway.
Evaluation and management of DMD gene copy number variations detected by prenatal SNP-array testing.
Hu J, Pang J, Hu R … +9 more , Zhou L, Yu W, Xi H, Luo Y, Yang S, Tang W, Hu A, Chen J, Peng Y
BMC Med Genomics · 2026 Mar · PMID 41792804 · Full text
OBJECTIVE: This study aims to evaluate the clinical management of incidental findings of copy number variations (CNVs) in the DMD gene detected through prenatal single nucleotide polymorphism array (SNP-array). METHODS:...
OBJECTIVE: This study aims to evaluate the clinical management of incidental findings of copy number variations (CNVs) in the DMD gene detected through prenatal single nucleotide polymorphism array (SNP-array). METHODS: Prenatal SNP-array testing was performed on samples exhibiting CNVs in the DMD locus, followed by parental analysis using the same technique. Additionally, multiplex ligation-dependent probe amplification (MLPA) testing was conducted on prenatal cases and their parents. Pregnancy outcomes were documented, and postnatal follow-up was conducted. RESULTS: SNP-array analysis identified copy number variations at Xp21 affecting either the entire DMD gene or only a portion of it in 14 fetuses. In 11 cases, MLPA testing confirmed the presence of deletions or duplications detected by the SNP-array. CONCLUSION: High-density SNP-array platforms with low reporting thresholds may incidentally detect a subset of exon-level copy number variations involving the DMD gene during routine prenatal testing and thereby contribute to early recognition of potential dystrophinopathy-related variants. Suspected DMD-related CNVs, especially exon-level alterations, require confirmation by targeted assays such as MLPA or next-generation sequencing, together with cautious clinical interpretation. Assessing the pathogenicity of prenatally detected DMD copy number variations remains challenging, particularly for duplications, which require careful evaluation. Furthermore, the sequential, time-intensive nature of confirmatory and familial studies often limits definitive risk assessment within the prenatal decision-making window, and introduces broader familial implications that must be navigated through careful, multidisciplinary counseling.
Prenatal diagnosis and clinical evaluation of fetuses with structural X chromosome abnormalities: a ten-year single-center retrospective study.
Zhang L, Zhuang J, Chen W … +2 more , Chen X, Huang N
BMC Med Genomics · 2026 Mar · PMID 41776513 · Full text
BACKGROUND: Structural X chromosome abnormalities are rare conditions and pose great challenges in prenatal genetic counseling. The present study aimed to identify and investigate the pregnancy outcome of fetuses with X...
BACKGROUND: Structural X chromosome abnormalities are rare conditions and pose great challenges in prenatal genetic counseling. The present study aimed to identify and investigate the pregnancy outcome of fetuses with X chromosome structural abnormalities in the Chinese population. METHODS: A total of 12 fetuses with X chromosome structural abnormalities were collected from 16,817 individuals who underwent prenatal diagnosis at Quanzhou Women’s and Children’s Hospital. Karyotype and/or chromosomal microarray analysis (CMA) were utilized to detect chromosomal abnormalities. RESULTS: Among the 12 fetuses with structural X chromosome abnormalities, one case had a balanced X; autosome chromosome translocation, the other 11 cases had unbalanced X; autosome or X-Y chromosome rearrangements. Eight subjects performed CMA detection, the CMA result was inconsistent with karyotype analysis result in Case 4, in which an additional 2q37.2q37.3 microduplication observed in the fetus. Finally, the karyotype of Case 4 was described as 46,X, der(X)t(X;2)(q22.3;q37.2). Parental origin verification was performed in 9 of the 12 cases, of which four cases were de novo and five cases inherited from the pregnant women. Prenatal ultrasound examination were available for 8 out of 12 cases, all the fetuses exhibited soft ultrasound abnormalities. CONCLUSION: The present study reports a series of 12 cases with structural X chromosome abnormalities. Our findings suggest that parental verification is valuable for guiding genetic counseling and managing pregnancy outcomes in fetuses with structural X chromosome abnormalities. In addition, CMA would be benefit for investigating the precise chromosome break points detected by karyotype analysis.
Identification of novel compound heterozygote variants in the PCCB gene in a fetus with undetectable fetal phenotype.
Feng X, Hu Y, Yan H … +4 more , Zhou L, Ma N, Xiong C, Xi H
BMC Med Genomics · 2026 Mar · PMID 41776507 · Full text
Propionic acidemia (PA) is a rare autosomal recessive metabolic disorder caused by functional deficiency of propionyl-CoA carboxylase, clinically characterized by life-threatening ketoacidosis, hyperammonemia, and multio...
Propionic acidemia (PA) is a rare autosomal recessive metabolic disorder caused by functional deficiency of propionyl-CoA carboxylase, clinically characterized by life-threatening ketoacidosis, hyperammonemia, and multiorgan dysfunction. Due to its nonspecific clinical manifestations, PA is frequently misdiagnosed or only identified during severe metabolic crises. This study reports a Chinese family with a history of offspring affected by PA. Through whole-exome sequencing and Sanger validation of fetal amniotic fluid and parental peripheral blood samples, two novel compound heterozygous variants in the PCCB gene were identified in the fetus, initially classified as variants of uncertain significance (VUS) per ACMG guidelines. Subsequent functional studies and amniotic fluid metabolomic analyses were performed. The results demonstrated that the paternal PCCB c.366_372 + 7del variant caused exon 3 skipping(p.Phe102_Gln124del) or exon 2–3 skipping (p.Gly62_Gln124del), while the maternal c.183 + 6T > G variant resulted in intron 1 retention (p.Gly62Valfs*10), both leading to protein truncation and aberrant mRNA splicing. Metabolomic analysis demonstrated significantly elevated C3 levels and an increased C3/C2 ratio, consistent with PA diagnosis. These novel PCCB splicing variants expand the mutational spectrum of PA and demonstrate the clinical utility of integrated genomic-metabolomic analysis for prenatal diagnosis and genetic counseling in high-risk PA families.
Genetic modulators of metabolic dysfunction-associated steatotic liver disease (MASLD) and their epistatic interactions: from in vitro and animal models to clinical outcomes.
Arriaga-González FG, de Jesús Castañeda-Córdova F, Díaz-Muñoz M … +4 more , Hoare M, Adams DJ, Robles-Espinoza CD, Molina-Aguilar C
BMC Med Genomics · 2026 Mar · PMID 41772607 · Full text
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as NAFLD (non-alcoholic fatty liver disease), is a growing global concern, affecting nearly a third of the world’s population. This umbre...
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as NAFLD (non-alcoholic fatty liver disease), is a growing global concern, affecting nearly a third of the world’s population. This umbrella term covers a range of liver pathologies, from reversible disease stages like simple steatosis, to irreversible conditions such as cirrhosis and hepatocellular carcinoma (HCC). MASLD, which may result from metabolic risk factors like obesity and type 2 diabetes, is projected to increase due to a rise in sedentary lifestyles. This review addresses genetic influences that predispose to disease development, including the role of risk-conferring and protective/preventive alleles. The epistatic relationships between genetic variants can significantly influence the development and progression of MASLD. Key genetic variants, such as those located in the PNPLA3, TM6SF2, and MBOAT7 genes, often interact to exacerbate MASLD severity and play key roles in lipid metabolism and liver inflammation. For example, the co-expression of certain PNPLA3 and TM6SF2 variants increases the risk of advanced fibrosis and HCC. Some variants located in HSD17B13 and MTARC1 offer protective effects, reducing the risk of severe liver disease despite comorbidities such as obesity, and can mitigate the harmful effects of these risk alleles. Additionally, the potential of polygenic risk scores (PRS) to predict MASLD development and its complications is also discussed, although challenges remain, particularly in underrepresented populations due to the lack of comprehensive catalogues of genetic variation. Understanding these complex gene-gene interactions and the role of the environment underscores the importance of considering epistatic relationships when assessing MASLD risk and developing personalized therapeutic strategies, which could ease the future burden on healthcare systems.
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