Diagnostics, Год журнала: 2024, Номер 14(23), С. 2709 - 2709
Опубликована: Ноя. 30, 2024
: Cardiomyopathy, including dilated cardiomyopathy (DCM) and hypertrophic (HCM), is a major cause of heart failure (HF) leading indication for transplantation. Of these patients, 20-50% have genetic cause, so understanding the basis will provide knowledge about pathogenesis disease diagnosis, treatment, prevention, counseling families.
Язык: Английский
Cell Metabolism, Год журнала: 2024, Номер 36(5), С. 1105 - 1125.e10
Опубликована: Март 20, 2024
A large-scale multimodal atlas that includes major kidney regions is lacking. Here, we employed simultaneous high-throughput single-cell ATAC/RNA sequencing (SHARE-seq) and spatially resolved metabolomics to profile 54 human samples from distinct anatomical regions. We generated transcriptomes of 446,267 cells chromatin accessibility profiles 401,875 developed a package analyze 408,218 metabolomes. find the same cell type, including thin limb, thick ascending limb loop Henle principal cells, display transcriptomic, accessibility, metabolomic signatures, depending on anatomic location. Surveying metabolism-associated gene revealed non-overlapping metabolic signatures between nephron segments dysregulated lipid metabolism in diseased proximal tubule (PT) cells. Integrating omics with clinical data identified PLEKHA1 as disease marker, its vitro knockdown increased expression PT differentiation, suggesting possible pathogenic roles. This study highlights previously underrepresented cellular heterogeneity underlying anatomy.
Язык: Английский
Процитировано
34
Molecular Neurobiology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 15, 2025
Abstract Tinnitus is the perception of sound without an external source, often associated with changes in auditory pathway and different brain regions. Recent research revealed overload missense variants ANK2 gene individuals severe tinnitus. , encoding ankyrin-B, regulates axon branching inhibits microtubule invasion. Missense mutations may promote excessive axonal formation excitatory synapses. This study aims to generate a patient-derived iPSC model from individual tinnitus differentiate these cells into otic-neural progenitors inner ear neurons. We successfully generated cellular through cell reprogramming. Using two-stage neural differentiation protocol, we differentiated neuron-like cells. confirmed expression genes, proteins, markers, including progenitors, qPCR immunostaining. Our analysis higher control line compared patient line. Although both lines formed multipolar neurons, displayed unique pattern closely grouped neurons increased neuronal projections dendrites control. provides valuable tool for studying molecular gene. It holds great promise development novel drug gene-based therapies
Язык: Английский
Процитировано
0
Reviews in Cardiovascular Medicine, Год журнала: 2025, Номер 26(1)
Опубликована: Янв. 15, 2025
Inherited cardiac arrhythmias, which may lead to sudden death, represent a significant health risk, with genetic factors playing key role in their development. The ankyrin 2 (ANK2) gene, encoding ankyrin-B, is implicated several heritable arrhythmia syndromes. ANK2 variants have been linked an inherited condition known as “ankyrin-B syndrome”, manifests spectrum of arrhythmias and cardiomyopathy. Our current review examines the relationship between specific heart conditions, summarizing recent findings on molecular mechanisms underlying ANK2-related structural abnormalities. By emphasizing need for further research, this aims enhance understanding ANK2’s disease guide development effective therapies.
Язык: Английский
Процитировано
0
JRSM Cardiovascular Disease, Год журнала: 2025, Номер 14
Опубликована: Янв. 1, 2025
The aim of this study was to report the spectrum genetic variations and clinical phenotype in a Vietnamese cohort with confirmed Brugada syndrome (BrS) using whole exome sequencing (WES). Fifty patients BrS were included study. Genomic DNA samples extracted from peripheral blood conducted for WES. variants annotated ANNOVAR. 13 reported genes associated filtered, predicted functional impact eight computational tools, classified according 2015 ACMG guidelines. Arrhythmic events documented one-fifth participants. Twenty-four probands identified carry 36 genes. Majority our SCN5A (9/36 variants, 25%), followed by KCNH2 (5/36 14%). prevalence carriers 16%; while minor gene less than 10%. Nine novel missense identified, including four (p.E901D, p.F853L, p.L377F, p.H184R), two ANK2 (p.S2845L V1497L), one CACNA1C variant (M1126V), DSP (p.K478N), intron splicing JUP (c.1498-5G>C). Our underscores primary significance BrS, as indicated prevalence, carrier rates, pathogenicity per classification, silico predictions, its correlation phenotypes. Longitudinal larger sample size, pedigree, Sanger sequence confirmation, analysis is recommended.
Язык: Английский
Процитировано
0
Epilepsia Open, Год журнала: 2025, Номер unknown
Опубликована: Фев. 17, 2025
Abstract The Ankyrin 2 ( ANK2 ) gene encodes the ankyrin‐B protein (ANKB), which is involved in organization and stability of membrane ion channels, transporters, receptors cardiomyocytes neurons. Variants genes are initially reported long QT syndrome autism. Animal models with deletion have exhibited seizures been anecdotally associated epilepsy case reports. Hereby, we a Taiwanese family pathogenic variant (chr4:114276707, c.6933del, p.T2312Lfs*2) that affects giant isoform. members presented young‐onset self‐limited focal epilepsy, achieved seizure‐free adulthood antiseizure medications. Interestingly, electrocardiogram revealed no obvious cardiac phenotype. We further reviewed ANK2‐related epilepsies. Most variants de novo loss‐of‐function variants. patients had young or neonatal seizures. Notably, most cases ‐related pharmaco‐responsive, suggests it likely to be underdiagnosed. With increased availability whole exome sequencing, diagnosis epilepsies may increase. co‐existence prolongation on electrocardiogram, autism, positive history arrhythmia sudden death provide important clues clinical epilepsy. Furthermore, correct genetic ANK2‐ related will initiate close surveillance avoid potential risk this disorder. Plain Language Summary has regarded as an arrhythmic gene. This study first familial highlighting role epileptogenesis. suggesting they Literature review phenotype genotype showed LOF tend CNS phenotypes, whereas missense arrhythmic. Early detection worthwhile considering
Язык: Английский
Процитировано
0
Cardiology Discovery, Год журнала: 2025, Номер unknown
Опубликована: Март 24, 2025
Abstract Congenital long QT syndrome (LQTS) is a life-threatening ion channelopathy caused by mutations in genes encoding specific channels, which can result malignant arrhythmia of the torsades de pointes type. LQTS type 4 represents less than 1% inherited cases, contrast to 90% attributable types 1–3, it specifically loss-of-function membrane-binding domain ANK2 . Here, novel variant ( c 2245 A>C, resulting p.Lys749Gln) associated with and Wolff-Parkinson-White was identified previously healthy 61-year-old male patient who suffered paroxysmal palpitations pre-syncope due recurrent pointes.
Язык: Английский
Процитировано
0
Neurobiology of Disease, Год журнала: 2025, Номер 209, С. 106908 - 106908
Опубликована: Апрель 14, 2025
Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by deficiency in the enzyme α-galactosidase A. This defect leads to progressive accumulation of glycosphingolipids, resulting kidney, heart, and nervous system damage, which contributes significant morbidity mortality. Early diagnosis essential prevent irreversible damage optimize treatment strategies. Recent research aims provide better understanding FD pathophysiology improve management approaches. study an international, multicenter, cross-sectional analysis that used RNA sequencing (RNA-seq) compare blood samples from 50 patients age- sex-matched healthy controls. The objective was identify gene expression patterns investigate secondary cellular pathways affected dysfunction. Among more than 400 differentially expressed genes detected, 207 were protein-coding genes, most overexpressed cohort. Functional enrichment highlighted processes related synaptic function, specifically concerning chemical transmission membrane potential regulation. Identified included those voltage-gated ion channels, neurotransmitter receptors, cell adhesion molecules, scaffold proteins, proteins associated with vesicles neurotrophic signaling, all linked lipid rafts. Notable identified encoding potassium channel (KCNQ2, KCNQ3, KCNMA1) ionotropic receptor involved glutamatergic (GRIN2A, GRIN2B) GABAergic systems (GABRA4, GABRB1, GABRG2, GABRQ). These findings suggest dysfunction defects FD, paving way for further into role pathology rafts underlying pathogenesis clinical outcomes FD.
Язык: Английский
Процитировано
0
Medical alphabet, Год журнала: 2025, Номер 4, С. 7 - 14
Опубликована: Апрель 21, 2025
Congenital long QT syndrome (LQTS) is the first described and most common inherited arrhythmia in absence of structural heart disease, which a predominantly autosomal dominant manner, characterized by an increased risk developing polymorphic ventricular tachycardia, syncope and/or seizures, sudden cardiac death. According to modern ideas about spectrum genetic variants that can contribute architecture LQTS, this disease cannot be considered as monogenic pathology. This supported presence not only pathogenic or likely canonical LQTS susceptibility genes, but also potentially proarrhythmic functional alleles poorly penetrating rare variants. Since genetically phenotypically heterogeneous timely verification diagnosis stratification arrhythmic events, well implementation genotype-specific therapeutic strategy, seem relevant.
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Март 27, 2024
Knowledge on the cell types and cell-specific gene expression of multicellular pathogens facilitates drug discovery allows gaining a deeper understanding pathogen biology. By utilizing single-cell RNA sequencing (scRNA-seq), we analyzed 19,581 cells globally prevalent parasitic flatworm, liver fluke Fasciola hepatica, which causes neglected tropical disease zoonosis known as fascioliasis. We identified 15 distinct clusters, including reproductive tract gastrodermis, report identification transcriptional characterization potential differentiation lineages stem within this parasite. Furthermore, previously unrecognized ELF5- TRPMPZQ-expressing muscle type was discovered, characterized by high protein kinases. Among these, p21-activated kinase PAK4 essential for parasite survival. These data provide novel insight into cellular composition complex demonstrate how at resolution can serve resource new targets.
Язык: Английский
Процитировано
2
Reviews in Cardiovascular Medicine, Год журнала: 2024, Номер 25(9)
Опубликована: Сен. 24, 2024
Atrial fibrillation (AF) is a common phenomenon of sustained arrhythmia leading to heart failure or stroke. Patients with mental disorders (MD), particularly schizophrenia and bipolar disorder, are at high risk AF triggered by the dysregulation autonomic nervous system, atrial stretch, oxidative stress, inflammation, electrical structural remodeling. Moreover, pathophysiological mechanisms underlying MD may also contribute genesis AF. An overactivated hypothalamic–pituitary–adrenal axis, aberrant renin–angiotensin–aldosterone abnormal serotonin signaling, disturbed sleep, genetic/epigenetic factors can adversely alter electrophysiology substrates, development In this review, we provide an update our collective knowledge molecular that link Targeting pathogenic MD-specific facilitate therapeutics mitigate cardiovascular mortality in patient population.
Язык: Английский
Процитировано
2