Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “precision diagnosis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2026

Multi-Omics Biomarker Signatures for Precision Diagnosis and Prognosis in Primary Liver Cancer: A Literature Review.

Primary liver cancer (PLC) is a biologically heterogeneous group of malignancies dominated by hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and a smaller subset of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), and its clinical burden remains high because current diagnostic and prognostic tools do not adequately capture molecular diversity. Conventional imaging, serum markers, and histopathological assessment remain insufficient for precise early diagnosis, subtype-resolved classification, and outcome stratification, while tissue and liquid biopsy approaches have expanded the range of analytes available for clinical assessment. Recent studies have identified candidate biomarker signatures across genomic, epigenomic, transcriptomic, proteomic, metabolomic, and circulating layers, suggesting that integrated multi-omics profiling may better represent tumor lineage, clonal evolution, immune context, and therapeutic vulnerability than isolated molecular readouts. However, these layers are not equally mature for clinical use: genomic testing is closest to routine therapeutic application in iCCA, plasma methylation assays are advancing for HCC surveillance augmentation, and many proteomic or metabolomic panels remain validation-stage tools. Their clinical value remains constrained by sampling bias, biospecimen-dependent signal loss, assay standardization, cost, and the need for prospective validation across clinically diverse populations. This narrative review critically synthesizes current evidence on multi-omics biomarker signatures for precision diagnosis and prognosis in primary liver cancer and argues that clinically useful signatures should be question-specific, stage-aware, and specimen-aware rather than universal multi-analyte panels.

Humans↗
PubMed2026

Novel insights into retinoblastoma: From oncogenic circuitry to precision diagnosis and eye-preserving therapies.

Retinoblastoma (RB) represents the most common primary intraocular malignancy in childhood and stands as a paradigm for translating molecular oncology into precision clinical management. This review synthesizes the comprehensive evolution in the understanding and treatment of RB. First, we deconstruct the intricate oncogenic circuitry that extends far beyond Knudson's classic "two-hit" RB1 inactivation model, describing non-classical MYCN-driven pathogenesis, multi-layered epigenetic reprogramming (including chromatin, RNA and histone changes), and distinct histological subtypes with defined clinical correlates, such as the favorable-prognosis cavitary RB. Single-cell genomics has elucidated the cellular origin from cone precursor cells and intratumoral heterogeneity. Risk stratification has been refined through well-defined classification systems, from the therapy-guiding International Intraocular Retinoblastoma Classification (IIRC) to the comprehensive American Joint Committee on Cancer Tumor-Node-metastasis (AJCC TNM) staging. Furthermore, the diagnostic paradigm has advanced from conventional anatomical imaging to liquid biopsies, enabling non-invasive molecular staging and monitoring via tumor-derived cell-free DNA analysis. Concurrently, the therapeutic landscape has undergone a radical shift, moving from enucleation and external-beam radiotherapy to an era dominated by local sight-preserving strategies. We provide a critical synthesis of the evidence for intravenous chemotherapy and the transformative role of super-selective intra-arterial chemotherapy (IAC), and describe essential randomized controlled trials, technical innovations, and optimized drug regimens. Finally, we explore emerging targeted molecular therapies and future directions. By integrating cutting-edge molecular insights with robust, high-level clinical evidence, this review offers the framework for achieving patient and eye survival as well as vision preservation in children with Retinoblastoma.

Intra-arterial chemotherapy↗
PubMed2026

Precision Diagnosis in APOL1 Kidney Disease With the p.N264K M1 Protective Variant.

IMPORTANCE: The APOL1 M1 (p.N264K) variant protects against G2-associated APOL1 focal segmental glomerulosclerosis (FSGS) and chronic kidney disease (CKD). However, the utility of knowing an individual's M1 status in guiding kidney disease diagnosis and other clinical scenarios remains underexplored. OBJECTIVE: To test 2 hypotheses: (1) in patients with APOL1 high-risk (HR) genotype kidney disease with at least 1 G2 allele, M1 can distinguish APOL1 CKD from non-APOL1 CKD; (2) in people with APOL1 low-risk (LR) genotypes, M1 is independently associated with protection against FSGS and CKD. DESIGN, SETTING, AND PARTICIPANTS: Retrospective case-control study using data from 2 tertiary care hospitals (Columbia University Irving Medical Center and Mass General Brigham Biobank) and population-based data (the UK Biobank [UKB], Electronic Medical Records and Genomics [eMERGE-III], and All of Us [AoU]). Participants were individuals with a diagnosis of FSGS or steroid-resistant nephrotic syndrome (SRNS), individuals with CKD, and controls. EXPOSURES: Exposures included the M1 variant (p.N264K) obtained from exome or genome sequencing data, sex, and genetic ancestry. MAIN OUTCOME AND MEASURE: The main outcome was the presence or absence of kidney disease, defined as FSGS or non-FSGS CKD, compared with non-kidney disease controls. Association between the M1 variant and disease status was assessed using odds ratios (ORs). RESULTS: A total of 107 696 individuals (54 994 [51.1%] female; 8779 [8.2%] with African ancestry, 78 475 [72.9%] with European ancestry, and 16 129 [15.0%] with multiethnic ancestry), including 3460 with FSGS or SRNS, 24 382 with non-FSGS CKD kidney disease, and 79 854 controls were enrolled in the discovery cohort. In the APOL1-HR group (1413 participants), M1 was significantly inversely associated with FSGS or SRNS cases compared with controls without kidney disease (OR, 0.20; 95% CI, 0.04-0.63; P = 3.69 × 10-3). Among individuals with CKD with APOL1-HR genotypes, M1 was 4 times more frequent in those whose CKD was not due to FSGS or SRNS. Importantly, electronic health record and biopsy review identified an alternative, non-APOL1 cause for CKD in nearly all APOL1-HR-M1 cases. There was no association between individuals with APOL1-LR genotypes with M1 and protection against CKD or FSGS. CONCLUSIONS AND RELEVANCE: In this case-control study of 107 696 individuals, presence of an APOL1-HR genotype M1 was significantly associated with protection against kidney disease, suggesting that it may have a role as a genetic modifier. Patients with CKD with an APOL1-HR genotype and M1 should be evaluated for an alternative and potentially treatable cause of their CKD.

Humans↗
PubMed2026

Identification of a G-quadruplex-forming cell-free DNA fragment as a biomarker for the precise diagnosis of hepatocellular carcinoma.

Early detection of hepatocellular carcinoma (HCC) remains challenging, as the currently recommended surveillance strategy based on ultrasound combined with alpha-fetoprotein (AFP) is limited by suboptimal sensitivity and accessibility. Cell-free DNA (cfDNA) provides a minimally invasive avenue for cancer detection. However, most existing cfDNA-based approaches either perform unreliably in low-input samples or require analytically complex workflows. Here, we systematically profiled serum cfDNA from individuals with HCC and without HCC and identified a high-abundance tumor-associated single cfDNA fragment at the FAM230F genomic region. Integrative analysis of liver assay for transposase-accessible chromatin with sequencing (ATAC-seq) data revealed consistent tumor-specific chromatin accessibility at this locus, suggesting a tumor-derived origin. Structural characterization further demonstrated enrichment of G-quadruplex (G4) features within the target sequence, which may increase resistance to serum nuclease degradation and promote its preferential retention in circulation. Based on these properties, we established a qPCR-based detection workflow with clinical accessibility. In a validation cohort independent of the discovery cohort, a ΔC t cutoff of 2 was selected by maximizing the Youden index within the same cohort. The assay showed a sensitivity of 94.5% and a specificity of 90.5% for distinguishing HCC from non-HCC. Collectively, our study identifies FAM230F as a structurally stable tumor-associated cfDNA fragment and establishes a simple and scalable qPCR-based assay for HCC detection, providing a practical framework for translating cfDNA fragment analysis into clinical biomarkers.

Journal Article↗
PubMed2025

Genomic mapping of diabetic kidney disease biomarkers and identification of potential inhibitors through virtual screening.

BACKGROUND: Diabetic kidney disease (DKD) is a common and serious complication of diabetes mellitus, marked by a multifactorial pathogenesis and the absence of sensitive diagnostic biomarkers. Identifying novel molecular targets and therapeutic options is essential to improve early diagnosis and treatment outcomes. METHODS: To uncover potential biomarkers and therapeutic candidates, we performed an integrated genomic analysis using microarray and RNA-seq datasets from the Gene Expression Omnibus (GEO) and Sequence Read Archive (SRA) databases. Differentially expressed genes (DEGs) were identified and subjected to protein-protein interaction (PPI) network analysis. Key genes were further explored through virtual screening of an FDA-approved compound library using molecular docking techniques. Drug-likeness was assessed via Lipinski's rule of five. RESULTS: A total of 40 DEGs were identified, among which ISCU (downregulated; involved in iron-sulfur cluster biogenesis) and AP1S2 (upregulated; associated with vesicular trafficking) emerged as potential biomarkers. PPI analysis revealed their involvement in critical DKD-related pathways, such as extracellular matrix remodeling and oxidative stress. Virtual screening identified six FDA-approved compounds with high binding affinity (≤-7.96 kcal/mol) to ISCU, notably ZINC000001576020, all of which complied with Lipinski's rule. CONCLUSIONS: This in-silico study nominates ISCU and AP1S2 as candidate diagnostic biomarkers for DKD and identifies computationally prioritized inhibitors targeting ISCU. These findings require experimental validation but provide a molecular framework for precision diagnosis and therapeutic development. These findings offer new molecular insights that could inform precision diagnosis and personalized treatment strategies for diabetic kidney disease.

Diabetic Nephropathies↗
PubMed2026

Ocular Nystagmus as the Initial Presenting Feature in a Patient with Complete CLTC Deletion: Expanding the Genotype-Phenotype Spectrum of CLTC-Related Disorder.

Background: CLTC-related neurodevelopmental disorder is a rare condition primarily characterized by global developmental delay (GDD) and intellectual disability (ID). To date, approximately 41 cases involving CLTC gene alterations have been reported. We present the first individual with a complete deletion of the CLTC gene. Methods: The proband is a male from a non-consanguineous family, presenting with congenital nystagmus, hypotonia, GDD, and autism spectrum disorder (ASD). Chromosomal microarray analysis and trio exome sequencing were performed. A systematic review of previously reported CLTC variant cases was conducted to delineate the phenotypic spectrum. Results: A de novo 363-kb heterozygous deletion at 17q23.1 spanning the entire CLTC gene was identified. The systematic review confirmed GDD/ID as core features and revealed various ocular abnormalities in a subset of cases. These findings indicate that the clinical phenotype extends beyond neurodevelopment, with multi-system involvement. Conclusions: The phenotypic heterogeneity of CLTC-related disorders underscores the need for comprehensive physical examination to identify extra-neurological manifestations. Accurate diagnosis relies on integrating detailed clinical phenotyping with comprehensive genomic testing. Early, precise diagnosis facilitates multidisciplinary management, informed genetic counseling, and the establishment of long-term surveillance protocols.

Humans↗
PubMed2026

Novel compound heterozygous POR variants in a neonate with Antley-Bixler syndrome and 46,XY DSD: a case report and literature review.

BACKGROUND: Cytochrome P450 oxidoreductase deficiency (PORD) is an ultra-rare autosomal recessive disorder within the congenital adrenal hyperplasia (CAH) spectrum, characterized by a broad clinical spectrum involving steroidogenesis defects, genital anomalies, and skeletal abnormalities. CASE PRESENTATION: We report a phenotypically female neonate with a 46,XY karyotype whose postnatal diagnostic evaluation was initiated after newborn screening revealed elevated 17-hydroxyprogesterone (17-OHP) concentration. The patient presented with mild hypertelorism, mild nasal hypoplasia, and low-set bilateral ears, along with female external genitalia consistent with disorder of sex development (DSD) and anal atresia. Radiological evaluation revealed femoral bowing and subsequent fracture. The craniofacial and skeletal abnormalities were consistent with the features of Antley-Bixler syndrome (ABS). Endocrine evaluation revealed elevated progesterone, markedly reduced testosterone, and secondary hyperaldosteronism. Genetic analysis identified three novel variants in the POR gene (NM_001395413.1): the patient harbored a paternal c.1187_1195dup (p.Pro396_Glu398dup) variant and two maternally inherited variants in cis, c.1447G>A (p.Gly483Ser) and c.1806 + 4_1806 + 28del. Protein structural modeling predicted that the p.Pro396_Glu398dup and p.Gly483Ser may disrupt the flavin adenine dinucleotide (FAD)-binding domain. RNA sequencing (RNA-seq) confirmed that the intronic variant c.1806 + 4_1806 + 28del caused aberrant splicing, resulting in partial intron retention and predicted impairment of the nicotinamide adenine dinucleotide phosphate (NADPH)-binding domain. According to American College of Medical Genetics and Genomics (ACMG) guidelines and incorporating functional evidence, c.1187_1195dup and c.1806 + 4_1806 + 28del were reclassified as likely pathogenic (LP), whereas c.1447G>A remained a variant of uncertain significance (VUS). CONCLUSIONS: This study describes a neonate with PORD caused by three novel POR variants and expands the known clinical spectrum of PORD by identifying rare manifestations including anal atresia and hearing loss. RNA-seq provided valuable functional evidence for variant interpretation and facilitated accurate molecular diagnosis. These findings highlight the importance of integrating genetic phasing, transcript-level functional analysis, and comprehensive clinical evaluation for precise diagnosis and counseling in rare endocrine disorders.

Humans↗
PubMed2026

Xp21 contiguous gene deletion syndrome presenting as congenital adrenal hypoplasia: molecular diagnosis and clinical re-evaluation of a pedigree.

OBJECTIVE: To investigate the molecular etiology in a male child clinically suspected of congenital adrenal hyperplasia (CAH) with negative conventional genetic testing, and to elucidate the genetic characteristics of his pedigree. METHODS: Clinical data from the proband and his family members were collected. Molecular diagnostics proceeded sequentially: initial targeted CAH testing (CYP21A2 and POR sequencing/MLPA, plus targeted NR0B1 CNV analysis) was followed by whole-exome sequencing coupled with genome-wide CNV analysis. RESULTS: The proband presented with neonatal cyanosis and hyperpigmentation. Laboratory tests showed markedly elevated ACTH (354.68 pmol/L) and low aldosterone (57.24 pg/mL). Molecular genetic testing identified a hemizygous deletion of approximately 4.44 Mb at Xp21.3-p21.1 (chrX:g.27080000_31520000), encompassing the NR0B1, GK, IL1RAPL1, and DMD genes. CNV-seq confirmed that the mother carried a heterozygous deletion of 4.38 Mb in the same region, while the father and four maternal aunts showed normal genotypes. CONCLUSION: This study ultimately diagnosed the proband with Xp21 contiguous gene deletion syndrome. The adrenal insufficiency resulted from X-linked congenital adrenal hypoplasia (AHC) due to NR0B1 haploinsufficiency, rather than CAH. These findings highlight the considerable clinical overlap between AHC and CAH, indicating that CNV analysis of the Xp21 region should be included in the diagnostic workup for male infants with suspected CAH but negative routine genetic testing. This provides a basis for the precise diagnosis and genetic counseling of such patients.

Humans↗
PubMed2026

A rapid CRISPR-based nanodroplet assay enables direct clinical identification of mycobacteria species.

The global incidence and mortality of nontuberculous mycobacterial infections have risen sharply with population aging. In some regions, they are now surpassing Mycobacterium tuberculosis complex infections, imposing a substantial clinical and economic burden. Because nontuberous mycobacteria exhibit species-level heterogeneity and require prolonged culture for identification, their diagnosis remains slow and is frequently inaccurate. Here, we describe a multiplexed clustered regularly interspaced short palindromic repeats (CRISPR)-assisted nanodroplet differential identification (CANDI) diagnostic platform that integrates species-agnostic target amplification with species-specific CRISPR-associated protein 12a (Cas12a) detection in fluorescence-barcoded nanodroplets. By spatially compartmentalizing CRISPR reactions into color-encoded nanodroplets, CANDI overcomes the multiplexing limitations of conventional CRISPR diagnostics and enables simultaneous interrogation of multiple mycobacterial targets in a single assay. We designed a 16-plex panel that distinguishes 15 clinically relevant Mycobacterium species and subspecies. CANDI achieved high analytical sensitivity and accurate discrimination in samples containing coinfections with multiple species or subspecies. When applied to 230 clinical specimens, including sputum, tracheal aspirates, and other respiratory fluids, CANDI delivered subspecies-level results within 3.5 hours, achieving 97.08% sensitivity and 99.7% specificity relative to culture-based identification. By combining multiplexed, high-specificity CRISPR detection with scalable droplet-based engineering, CANDI has the potential to overcome the culture dependency of current diagnostics and enable species- and subspecies-level identification across the genetically complex Mycobacterium genus, offering a clinically adaptable framework for rapid, precision diagnosis of mycobacterial infections.

Humans↗
PubMed2025

Alzheimer's subtypes A supervised, unsupervised, multimodal, multilayered embedded recursive (SUMMER) AI study.

Since Alzheimer's disease (AD) is a heterogeneous disease, different subtypes may have distinct biological, genetic, and clinical characteristics, requiring tailored interventions. While several proposed subtypes of AD exist, there is still no clear consensus on a definitive classification. By leveraging complementary AI approaches, including supervised and unsupervised learning, within a recursive pipeline (SUMMER) that integrates multimodal datasets encompassing MRI measurements, phenotypes, and genetic data, our goal was to generate robust scientific evidence for identifying AD subtypes. Data was downloaded from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and included neuroimaging data (MRI), genetics (SNPs), clinical diagnosis, and demographics. 1133 European American participants' images, aged 55-95, were included in this study. The analysis was multi-fold, where the first step involved applying an unsupervised application to a subset of the MRI sample (AD + cognitively normal (CN) aged matched groups, 100 men aged 68-85 years, and 76 women aged 68-85 years). The MRI brain gray matter was segmented into 44 regions of interest (ROIs) according to a standard atlas, and 618 features were extracted, including ROI voxel intensity measurements such as minimum, maximum, and histogram variables. Results identified a cluster of subtype AD men and a cluster of subtype AD women that were distinct from the rest of their respective samples. In the next step, the integrity of the identified subtype AD clusters was investigated using the XGBoost supervised machine learning application with genetic features (SNPs, N=36,724) and labels: the identified subtype AD cluster vs. the rest of the sample, stratified by sex. A significant AD subtype men model (accuracy=0.85, F1=0.72, AUC=0.83) and a significant women AD subtype model (accuracy=0.81, F1=0.81, AUC=0.81) were built, confirming the homogeneity of the isolated AD subtype clusters. Discriminative biomarkers were extracted from the significant models, including selected ROIs and SNPs. Finally, the subtype models were tested on an unseen subset of ADNI data. The genetic-based models identified clusters of AD subtype participants consisting of 34% of the men AD group and 47% of the women AD group. Phenotypic analysis indicates that lower body weight was associated with the women's AD subtype. Complex diseases like AD demand a sophisticated, multimodal approach for precise diagnosis. Effectively identifying disease subtypes enhances the potential for personalized treatment, ultimately improving patient outcomes.

Journal Article↗
PubMed2026

Early infantile developmental and epileptic encephalopathy: clinical spectrum, diagnosis, outcomes, and evolving treatment strategies.

Early infantile developmental and epileptic encephalopathy (EIDEE) is among the most severe epilepsy syndromes, with onset before three months of age and an estimated incidence of approximately 10 per 100,000 live births. The 2022 International League Against Epilepsy classification unified the historically distinct Ohtahara syndrome and early myoclonic encephalopathy under a single diagnostic framework defined by frequent drug-resistant tonic and/or myoclonic seizures, an abnormal neurological examination, and an abnormal interictal electroencephalogram-most characteristically a burst-suppression pattern. This narrative review synthesizes the clinical, electrophysiological, neuroimaging, genetic, and therapeutic literature within the EIDEE framework. The clinical phenotype is characterized by central hypotonia, postnatal microcephaly, cortical visual impairment, and age-dependent syndromic evolution toward infantile epileptic spasms syndrome or Lennox-Gastaut syndrome in the majority of patients. Electroencephalography remains essential for syndromic classification, while systematic metabolic screening and early trio whole-exome or whole-genome sequencing are central to the etiologic workup, achieving diagnostic yields of 60-65%. The most commonly identified genetic causes include STXBP1, KCNQ2, and SCN2A variants. Outcomes are poor overall and strongly etiology-dependent: vitamin-responsive disorders carry a substantially more favorable prognosis, whereas mortality reaches 25% in genetic cohorts. Genotype-guided pharmacotherapy is now applicable to a clinically meaningful subset of patients, with sodium channel blockers, potassium channel openers, and emerging antisense oligonucleotide therapies representing important therapeutic advances. Gene therapy trials are underway but have encountered early safety signals, underscoring the vulnerability of this population. Critical unmet needs include earlier molecular diagnosis, precision therapies targeting developmental outcomes beyond seizure control, and prospective international registries to characterize the long-term natural history of EIDEE.

Humans↗
PubMed2026

Omics in optic neuropathies: From molecular landscapes to personalized therapeutics.

Optic neuropathies comprise a heterogeneous group of disorders involving transient or permanent injury to retinal ganglion cells (RGCs) and their axons. Clinically, these neurodegenerative conditions manifest as dyschromatopsia, decreased visual acuity, and visual field defects, and in severe cases may ultimately lead to blindness and disability. The marked heterogeneity across disease subtypes, incompletely understood etiologies, and complex pathogenic mechanisms pose substantial challenges to precise diagnosis and effective treatment. Recent advances in omics technologies - including genomics, transcriptomics, proteomics, metabolomics, lipidomics, single-cell and spatial sequencing, and integrative multi-omics approaches - have ushered optic nerve degenerative disease research into an era of high-resolution comprehensive investigation. In this review, we summarize representative applications of omics approaches to elucidate genetic alterations, signaling dysregulation, metabolic reprogramming, and immune responses in optic neuropathies. We further discuss the emerging potential of multi-omics in identifying early diagnostic biomarkers and informing individualized therapeutic strategies. Finally, we provide a forward-looking perspective on the future trajectory of omics technologies and their prospects in both fundamental research and clinical translation, with the overarching aim of accelerating the bench-to-bedside transition in this critical eye disease field.

biomarkers↗
PubMed2026

Chinese expert consensus on precision testing and molecular diagnosis of pancreatic cancer (2025).

This consensus by the CSCO Pancreatic Cancer Expert Committee establishes evidence-based guidelines for molecular testing in pancreatic ductal adenocarcinoma. It details recommendations for biomarkers (e.g., KRAS, BRCA, MSI), liquid biopsy, and precision imaging to direct targeted therapies and immunotherapy, aiming to standardize diagnosis and optimize individualized patient care. Pancreatic ductal adenocarcinoma (PDAC) is the most common pathological type of primary pancreatic malignancy, accounting for ~95% of cases and generally referred to as pancreatic cancer [1]. Its prognosis is extremely poor and its incidence continues to rise [2]. According to the most recent global cancer statistics, the incidence of pancreatic cancer ranks 12th among all cancers, and its mortality ranks 6th, making it one of the deadliest malignancies worldwide [3]. Approximately 57% of patients have metastatic disease at diagnosis and require systemic therapy, for which chemotherapy remains the standard first-line option [1]. However, the overall response rate to currently available systemic regimens is low, and the 5-year survival rate for patients with metastatic disease remains below 5% [3]. Although most pancreatic cancers harbor canonical driver mutations, they exhibit marked heterogeneity at the molecular level. Whole-genome sequencing (WGS) and integrative genomic analyses have identified molecular subtypes of PDAC with potential clinical relevance [4-9]. With the increasing implementation of precision oncology, the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Pancreatic Cancer give a level 1 recommendation to perform genetic and other molecular testing on tissue or cytologic specimens as part of the pathological diagnostic work-up, in order to guide individualized treatment, including targeted therapy and immunotherapy [10]. To further promote the use of genetic and molecular testing in the precision treatment of pancreatic cancer, the CSCO Pancreatic Cancer Expert Committee convened a multidisciplinary panel to develop the present Chinese Expert Consensus on Precision Testing and Molecular Diagnosis of Pancreatic Cancer (2025), aiming to provide clinicians with an authoritative reference for precision diagnostics and treatment decision-making.

Humans↗
PubMed2026

Guidelines for Genetic Testing of Peripheral Nerve Disorders.

Inherited peripheral neuropathies (IPNs) comprise a clinically and genetically heterogeneous group of disorders affecting approximately 1 in 2500 individuals and represent one of the most common inherited neurologic diseases. The rapidly expanding identification of disease-causing genes and the widespread implementation of next-generation sequencing (NGS) have fundamentally transformed the diagnostic evaluation of these disorders. Contemporary molecular testing has substantially increased diagnostic yield, shortened the diagnostic delay, refined disease classification, and strengthened genotype-phenotype correlations. In the United States, NGS-based multigene panels have become the most cost-effective first-line molecular diagnostic approach for most patients with suspected inherited neuropathies, whereas phenotype-directed single-gene testing remains appropriate in selected clinical circumstances and in healthcare systems in which access to comprehensive sequencing is limited. Despite these advances, challenges continue to affect diagnostic accuracy, including interpretation of variants of uncertain significance, detection of copy number variants and repeat expansions, technical limitations associated with highly homologous genomic regions such as SORD, and variability in gene content and analytic performance among commercially available testing platforms. Accurate diagnosis therefore requires integration of clinical phenotype, electrodiagnostic findings, family history, and molecular data. Establishing a precise genetic diagnosis has become increasingly important because it improves prognostic accuracy, guides genetic counseling and cascade testing, identifies patients with treatable hereditary neuropathies such as transthyretin amyloidosis, and facilitates enrollment in gene-specific clinical trials and emerging precision therapies. An evidence-based, phenotype-driven approach that incorporates contemporary molecular technologies is essential to maximize diagnostic efficiency while recognizing the strengths and limitations of currently available genetic testing strategies.

Charcot–Marie–tooth disease↗
PubMed2026

Prenatal exome sequencing of fetuses with central nervous system anomalies based on prenatal ultrasound and magnetic resonance imaging diagnosis: A retrospective cohort study with a systematic review and meta-analysis.

INTRODUCTION: Fetal central nervous system (CNS) abnormalities have diverse etiologies, with genetic factors as a major contributor. Prenatal exome sequencing (ES) is a powerful tool for precise molecular diagnosis of CNS anomalies, but its diagnostic yield varies among studies. This study aimed to evaluate the additional diagnostic yield of prenatal ES compared with chromosomal microarray analysis (CMA) in fetuses with CNS anomalies detected by prenatal imaging. MATERIAL AND METHODS: We collected ES results from fetuses diagnosed with CNS anomalies by prenatal imaging (2019-2024) who had negative results. Subgroup analyses assessed phenotype-specific ES diagnostic yield for associated genes and variants. A systematic review and meta-analysis incorporating our data and published studies further explored the association between phenotype and diagnostic yield. RESULTS: In the cohort study of 219 cases, ES identified pathogenic/likely pathogenic single nucleotide variations in 36 cases (16%). The highest diagnostic yield of ES was in cases with multisystem malformations (25%, 14/55), followed by multiple CNS anomalies (15%, 2/13) and isolated CNS anomalies (13%, 20/151). The most commonly identified isolated CNS anomaly was agenesis of the corpus callosum (31%, 5/16). Neural tube defects with urogenital anomalies were associated with a positive ES finding in 57% (4/7) of cases. The meta-analysis of 989 cases from 22 studies showed a pooled diagnostic yield of ES of 27% (95% CI, 21%-34%). The highest diagnostic yield of ES was in cases of corpus callosum anomalies with facial abnormalities (75%, 8/11) and neural tube defects with urogenital malformations (80%, 12/15). The diagnostic yield of ES for three or more CNS abnormalities was 43% (95% CI, 31%-58%), significantly higher than that for only two abnormalities (10%, 95% CI, 4%-18%). No significant difference in diagnostic yield was found between cases identified by prenatal MRI combined with ultrasound (27%, 95% CI, 20%-36%) and those identified by ultrasound alone (25%, 95% CI, 17%-35%). CONCLUSIONS: ES provided a significantly higher diagnostic yield than CMA for fetal CNS abnormalities, with diagnostic yields varying by phenotype. The systematic review and meta-analysis confirmed that the complexity and combination of malformations are key factors associated with differences in ES diagnostic yield.

Humans↗
PubMed2026

Integrated Bioinformatics Analysis Revealing that the NSDHL Gene Might Be Associated with the Progression of Western HFD/SW-Induced Hepatocellular Carcinoma.

BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC) remains a significant global health concern. However, the etiology and pathogenesis of HCC have yet to be fully elucidated. Previous studies have indicated a close association between obesity and the occurrence and progression of HCC. The objective of this study was to employ bioinformatics strategies in order to explore key genes associated with the clinical diagnosis and prognosis of HCC induced by a Western high-fat diet and sugar water (HFD/SW). MATERIALS AND METHODS: We obtained the expression profile chip data GSE197884 from the Gene Expression Omnibus (GEO) database. Subsequently, “DESeq” and “Limma” R packages were employed to identify differentially expressed genes (DEGs) while constructing a co-expressed gene network using weighted gene co-expression analysis (WGCNA). Functional enrichment analyses were then carried out, followed by the construction of a protein-protein interaction (PPI) network to uncover core genes. The core genes were confirmed through data retrieved from The Cancer Genome Atlas (TCGA) database in order to determine their status as hub genes. Finally, survival and tumor immune infiltration analyses were performed to unveil the prognostic significance of these hub genes. RESULTS: In total, 126 intersection targets were retrieved through the Venn diagram. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the DEGs were primarily related to the proliferation and apoptosis of HCC cells, the digestion and metabolism of liver cells, the HCC tumor microenvironment, and immune response. The PPI network analysis identified 11 core targets, among which seven hub genes, including NSDHL, MVK, SQLW, GCAT, ALAS2, GLDC, and AGXT, were obtained after TCGA database validation. Furthermore, it was found that NSDHL was closely associated with the clinical diagnosis and prognosis of HCC induced by HFD/SW and also affected the cellular immune infiltration in the HCC tumor microenvironment. CONCLUSION: The present study demonstrated a significantly elevated expression of NSDHL in HCC tissues, suggesting its potential as a specific biomarker for precise clinical diagnosis and prognosis assessment of HCC induced by HFD/SW.

Computational Biology↗
PubMed2026

Precision medicine and parental experience: a longitudinal study of psychosocial responses to germline genomic results in pediatric oncology.

INTRODUCTION: Precision medicine has become central to pediatric oncology, with germline genomic sequencing commonly integrated into routine care. Families must interpret complex genomic findings during emotionally vulnerable periods, generating mixed reactions ranging from clarity and relief to anxiety and uncertainty. Palliative care clinicians, genetic counselors, psychologists, social workers, and oncology providers may each contribute to supporting families as they interpret and integrate these findings over the course of a child's cancer care and beyond. Little is known about the trajectory of parental emotional and cognitive responses after receiving germline sequencing results, limiting clinicians' ability to anticipate support needs across the cancer care continuum. This study quantitatively examines parental emotional and cognitive responses across time following disclosure of germline sequencing results in a pediatric oncology setting. METHODS: Parents (n = 218) self-reported sequencing-related distress, positive feelings, intrusive thoughts, certainty, and self-efficacy using validated measures at two longitudinal follow-up points after disclosure of their child's germline test results. Outcomes were compared across germline test result types (pathogenic/likely pathogenic [P/LP], n = 31 [14%]; variants of uncertain significance [VUS], n = 86 [39%]; and negative, n = 101[46%]). RESULTS: Parents of children receiving P/LP or P/LP+VUS results reported significantly higher distress yet greater positive feelings than parents receiving negative results. Notably, certainty and self-efficacy increased from Timepoint 1 (median 254 days following return of results) to Timepoint 2 (median 537 days). Intrusive thoughts did not significantly differ by genetic result type or change over time; however, the factors contributing to intrusive thoughts could not be determined from the current study. DISCUSSION: These findings provide insight into how families adapt to germline genomic information following a pediatric cancer diagnosis. As precision medicine becomes increasingly embedded in pediatric oncology, structured follow-up and communication that address families' evolving informational and psychosocial needs are essential to ensure care that is scientifically precise, emotionally attuned, and centered on the family experience.

family-centered care↗
PubMed2026

A G-Quadruplex-Activated Near-Infrared Chemiluminescent Probe for In Situ Hepatic Imaging of the Hepatitis C Virus Genome.

Real-time monitoring of viral replication is essential for infectious disease diagnosis and antiviral drug development. The G-quadruplex (G4), a conserved regulatory element within viral genomes, represents a significant endogenous biomarker for tracking viral activity. However, imaging viral G4s in deep tissues remains a challenge for current optical technologies due to severe photon attenuation and autofluorescence. Herein, we report Lumin680, the first near-infrared (NIR) chemiluminescent probe directly activated by conserved viral G4 conformations. Its chemiluminescence was triggered by parallel G4, emitting in the NIR optical window (680 nm) with a 104.6-fold signal enhancement. Notably, the luminescence of Lumin680 could penetrate up to 1.2 cm of biological tissue, outperforming traditional G4 fluorescent probe. In vivo, Lumin680 enabled the rapid visualization of orthotopic hepatitis C virus (HCV) genome RNA-presenting mini-organ within 5 min post-intravenous administration. Furthermore, the chemiluminescent intensity of Lumin680 quantitatively mapped the therapeutic efficacy of clinical direct-acting antivirals (DAAs) at both the cellular and whole-animal levels, exhibiting high concordance with the gold-standard quantitative RT-PCR (qPCR). This study not only provides a powerful G4 specific chemiluminescent tool but also establishes a novel paradigm for the non-invasive, in situ diagnosis and precise therapeutic monitoring of viral infections.

G-Quadruplexes↗