Geno'X Veille
@genox-veille.fr
Weekly clinical genomics literature watch · curated by Dr Thibaut Benquey, medical biologist (genetics). New genes · pharmacogenomics · hereditary cancer · bioinformatics. New picks every Wednesday. Free, no ads. → genox-veille.fr
NAT2 encodes arylamine N-acetyltransferase 2, a phase II enzyme acetylating arylamines and arylhydrazines including isoniazid, and its extensive polymorphism explains the variable distribution of rapid and slow acetylators across populations. #pharmacogenomics #PGx #genomics
Clinical Function Assignment of NAT2 Alleles by the Clinical Pharmacogenetics Implementation Consortium Pharmacogene Cur
NAT2 acetylator status and drug response · Clin Pharmacol Ther 2026
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This real-life, retrospective, multicenter study assessed the germline testing landscape in men referred for genetic counselling because of prostate cancer, and the added benefit of next-generation sequencing (NGS) over founder variant testing alone. #genomics #HereditaryCancer #ClinicalGenetics
Identifying and characterizing the germinal genetic landscape of men with prostate cancer: A real-life, retrospective, m
Prostate cancer — germline predisposition · Genet Med Open 2026
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CYP2C19 genotyping is recommended to guide antiplatelet selection after ischaemic stroke or TIA; this study quantifies exposure to other CYP2C19 substrates in the same patients. #pharmacogenomics #PGx #genomics
Exposure to CYP2C19-metabolized drugs following acute stroke: A longitudinal cohort study to inform implementation of CY
Ischaemic stroke — exposure to CYP2C19 substrates · Br J Clin Pharmacol 2026
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Variants in small nuclear RNA (snRNA) genes are an emerging cause of Mendelian disease, particularly neurodevelopmental disorders, but remain out of reach of conventional WES, which does not capture these loci. #genomics #ClinicalGenetics #RareDisease
Whole-genome discovery of pathogenic snRNA variants and efficient extended-exome screening.
Unsolved Mendelian disorders, neurodevelopmental disorders · iScience 2026
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Missense variants in the BRCA1 RING domain account for a large share of the variants of uncertain significance (VUS) reported in cancer genetics, providing no information usable for clinical decision-making. #genomics #HereditaryCancer #ClinicalGenetics
Assessing the Clinical Relevance of BRCA1 RING Domain Variants of Uncertain Significance.
Hereditary breast and ovarian cancer (HBOC) · Curr Oncol 2026
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The authors describe a hypermethylated CCG repeat expansion at Xp22, in the 5'UTR of BCLAF3, in males with neurodevelopmental disorders. #genomics #ClinicalGenetics #RareDisease
Multiomic approaches identify a rare CCG repeat expansion in BCLAF3 in neurodevelopmental disorders.
X-linked neurodevelopmental disorder · Genome Med 2026
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The authors describe a generic algorithm that reconstructs allele sequences from long amplicon reads (Oxford Nanopore) using a “sequence-first” approach: rather than calling variants directly, it reconstructs the underlying sequences de novo, then compares them t… #bioinformatics #genomics #compbio
A De Novo Algorithm for Allele Reconstruction from Oxford Nanopore Amplicon Reads, with Application to CYP2D6.
Allele reconstruction and diplotyping from long-read amplicon data · Bioinformatics 2026
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This prospective randomized controlled trial evaluated whether pharmacogenomics-guided therapy improves blood pressure control in 900 hypertensive patients, allocated to conventional care (n = 450) or guided therapy (n = 450) with testing of six loci (CYP2D6, CYP2C… #pharmacogenomics #PGx #genomics
Preliminary Application of Antihypertensive Gene Detection in the Treatment of Hypertension.
Arterial hypertension (antihypertensive therapy) · Med Sci Monit 2026
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AAVC is a new tool for automated variant classification following ACMG standards and ClinGen specifications, leveraging large public databases and in silico predictors. #bioinformatics #genomics #compbio
AAVC: an automated framework for high-accuracy ACMG-based variant classification.
Automated variant interpretation (ACMG classification) · Genet Med 2026
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This study identifies KATNA1, encoding the p60 subunit of katanin, as a previously unrecognised cause of autosomal dominant macular dystrophy. #genomics #ClinicalGenetics #RareDisease
Missense variants in KATNA1 alter microtubule dynamics and underlie dominant macular dystrophy.
Dominant macular dystrophy (inherited retinal disease) · Res Sq 2026
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Hereditary diffuse gastric cancer with germline CDH1 variants carries a high risk of signet ring cell carcinoma (SRCC), with limited data to choose between endoscopic surveillance and prophylactic total gastrectomy. #genomics #HereditaryCancer #ClinicalGenetics
Predictors of early cancer burden in CDH1 pathogenic variant carriers: a UK single-centre cohort study.
Hereditary diffuse gastric cancer (HDGC) · EClinicalMedicine 2026
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Time in therapeutic range (TTR) on warfarin is frequently suboptimal in patients supported with a HeartMate 3 left ventricular assist device, increasing bleeding and thromboembolic risk. #pharmacogenomics #PGx #genomics
Optimizing Time in Therapeutic Range in Patients With HeartMate 3: Pharmacist-Led Anticoagulation Using Pharmacogenetics
Warfarin anticoagulation (HeartMate 3 left ventricular assist device) · Ann Pharmacother 2026
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Cohesin release factors (WAPL, PDS5A, PDS5B) had never been tied to Mendelian disease. #genomics #ClinicalGenetics #RareDisease
Clinical, in vitro, and in vivo evidence of WAPL as a cohesinopathy-associated gene and phenotypic driver of 10q22.3q23.
WAPL-related neurodevelopmental disorder and 10q22.3q23.2 genomic disorder · Am J Hum Genet 2026
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The NT-MBGT programme tested 3515 unselected, newly diagnosed breast cancer patients across 14 NHS units through a clinician-light 'BRCA-DIRECT' mainstreaming pathway (home saliva testing, postal consent, access to a genetic counsellor telephone helpli… #genomics #HereditaryCancer #ClinicalGenetics
Routine germline genetic testing in 3552 unselected NHS breast cancer patients: evidence informing testing criteria and
Hereditary breast cancer · NPJ Breast Cancer 2026
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This study leverages a genomic database (LODB) enriched for consanguinity and founder effects to accelerate validation of still-tentative gene-disease relationships (GDR). #genomics #ClinicalGenetics #RareDisease
High Throughput Evidence Generation to Support Tentative Gene Disease Relationship from A Cohort Enriched for Autozygosi
Recessive Mendelian disorders (cohort enriched for consanguinity) · Genet Med 2026
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Molecular diagnosis of imprinting disorders relies on sequential assays that are expensive, slow and often insufficient for detecting mosaicism. #bioinformatics #genomics #compbio
Targeted long-read sequencing with adaptive sampling enables the integrated genomic and epigenomic profiling of imprinti
Imprinting disorder diagnostics (Beckwith-Wiedemann spectrum) · Sci Rep 2026
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CYP2D6-mediated bioactivation of tamoxifen to endoxifen determines its efficacy, but the structurally complex alleles common in Asia complicate conventional genotyping. #pharmacogenomics #PGx #genomics
Resolving CYP2D6 Structural Complexity with Long-Read Sequencing: Implications for Tamoxifen Precision Dosing in Thai Br
CYP2D6 pharmacogenetics (tamoxifen) · Clin Pharmacol Ther 2026
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Pathogenicity predictors exceed 0.97 AUROC, yet the monogenic-epilepsy VUS backlog persists because pathogenicity alone gives neither direction of effect nor a link to treatment. #bioinformatics #genomics #compbio
From Pathogenicity to Mechanism: A Variant Interpretation Framework for Monogenic Epilepsy.
Variant interpretation — monogenic epilepsy · Clin Genet 2026
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Ménière disease, a chronic inner-ear disorder (recurrent vertigo, fluctuating sensorineural hearing loss, tinnitus), remains poorly understood. #genomics #ClinicalGenetics #RareDisease
Genome-wide analysis implicates inner ear development in Ménière disease.
Ménière disease · Am J Hum Genet 2026
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More than 80% of patients meeting hereditary breast and ovarian cancer (HBOC) criteria carry no pathogenic variant in BRCA1, BRCA2 and other core genes. #genomics #HereditaryCancer #ClinicalGenetics
Multi-omics analysis in suspected hereditary breast and ovarian cancer cases reveals novel candidate susceptibility fact
Hereditary breast and ovarian cancer (HBOC) · NPJ Breast Cancer 2026
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This study investigates the genetic determinants of the pharmacokinetics of CYP2C8 substrates (repaglinide, gemfibrozil) in healthy volunteers. Sequencing data reveal a novel functional allele, CYP2C819 (rs2071426), predicted to create an intronic splice donor site. #pharmacogenomics #PGx #genomics
Identification of a Functional CYP2C8 Variant Allele that Alters Splicing, Reduces Protein Expression, and Increases Dru
CYP2C8 pharmacogenetics (repaglinide, gemfibrozil) · Clin Pharmacol Ther 2026
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CDK20 (also known as CCRK), a cyclin-dependent kinase regulating primary cilium structure and Sonic Hedgehog signalling, had not previously been linked to any human disorder. #genomics #ClinicalGenetics #RareDisease
Bi-allelic variants in CDK20 cause a severe ciliopathy with midline brain and facial anomalies.
Severe ciliopathy with midline brain and facial anomalies · Am J Hum Genet 2026
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This mechanistic study shows that BRCA1 deficiency strongly increases choline metabolism in ovarian cancer, beyond its canonical role in DNA repair. #genomics #HereditaryCancer #ClinicalGenetics
Choline metabolism drives metastasis in BRCA1-deficient ovarian cancers by activating FAM3C
BRCA1-deficient ovarian cancer — metastasis · Nat Commun 2026
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The diagnostic yield of a WES/WGS-based 51-gene virtual panel plus mitochondrial DNA was assessed in 62 partially pre-screened patients with hereditary optic atrophy. #genomics #ClinicalGenetics #RareDisease
Diagnostic Yield and Clinical Impact of Comprehensive WES/WGS Testing Beyond Common Genetic Causes in Hereditary Optic A
Hereditary optic atrophy · Clin Genet 2026
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This study directly compares long-read (lrGS) and short-read (srGS) WGS in 310 families with undiagnosed neurological disorders from the Hong Kong Genome Project. #bioinformatics #genomics #compbio
Systematic evaluation of long-read and short-read sequencing in neurological disorders diagnosis: a direct comparison st
Genetic neurological disorders — direct comparison of long-read vs short-read WGS · NPJ Genom Med 2026
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The UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI-PGx) publishes a guideline for HLA genotyping before prescribing carbamazepine, oxcarbazepine or eslicarbazepine. #pharmacogenomics #PGx #genomics
HLA genotype testing for carbamazepine, oxcarbazepine and eslicarbazepine: A guideline developed by the UK Centre of Exc
Hypersensitivity to carbamazepine, oxcarbazepine and eslicarbazepine — HLA genotyping · Br J Clin Pharmacol 2026
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AI-CURA is an LLM framework that nearly fully automates genetic variant classification per ACMG/AMP and ClinGen recommendations, separating assessment of non-literature criteria (standard bioinformatic tools) from assessment of literature-based evidence (handled… #bioinformatics #genomics #compbio
AI-CURA, an automated LLM workflow for high-accuracy genetic variant classification
Automated genetic variant classification by LLM following ACMG/AMP/ClinGen · Sci Transl Med 2026
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A systematic approach to detect homozygous copy number losses was applied to exome data from 2,021 Indian patients with suspected Mendelian disorders. #genomics #ClinicalGenetics #RareDisease
Systematic analysis of homozygous autosomal copy number losses in exomes improves diagnostic yield and uncovers ultra-ra
Ultra-rare recessive disorders — homozygous copy number losses on exome · Eur J Hum Genet 2026
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The randomised phase 3 SUBITO trial (174 patients, including germline BRCA1/2 carriers) compared intensified alkylating chemotherapy with autologous stem cell rescue to standard chemotherapy followed by one year of olaparib, in stage III HER2-negative… #genomics #HereditaryCancer #ClinicalGenetics
Targeting homologous recombination deficiency with intensified chemotherapy versus standard chemotherapy followed by ola
Stage III HER2-negative breast cancer with HRD / germline BRCA1/2 mutation · Lancet Oncol 2026
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This retrospective study of 126 hematopoietic stem cell transplant recipients analyzes the joint effect of CYP2C19 genotype and inflammation (CRP) on voriconazole exposure. #pharmacogenomics #PGx #genomics
Inflammation-driven variability in drug metabolism: Insights from voriconazole treatment of HSCT recipients
Voriconazole after hematopoietic stem cell transplantation — inflammation-driven phenoconversion · Br J Clin Pharmacol 2026
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