Diagnostics, Journal Year: 2024, Volume and Issue: 14(23), P. 2709 - 2709
Published: Nov. 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.
Language: Английский
Journal of the American College of Cardiology, Journal Year: 2025, Volume and Issue: 85(7), P. 727 - 740
Published: Feb. 1, 2025
Language: Английский
Citations
4
Environmental Science & Technology, Journal Year: 2024, Volume and Issue: 58(17), P. 7256 - 7269
Published: April 19, 2024
Through investigating the combined impact of environmental exposures experienced by an individual throughout their lifetime, exposome research provides opportunities to understand and mitigate negative health outcomes. While current is driven epidemiological studies that identify associations between effects, new frameworks integrating more substantial population-level metadata, including electronic administrative records, will shed further light on characterizing exposure risks. Molecular biology offers methods concepts study biological impacts exposomes in experimental computational systems. Of particular importance growing use omics readouts clinical studies. This paper calls for adoption mechanistic molecular approaches as essential step understanding genotype interactions underlying human phenotypes. A series recommendations are presented make necessary appropriate steps move from association causation, with a huge potential inform precision medicine population health. includes establishing hypothesis-driven laboratory testing within field, supported read across model systems human.
Language: Английский
Citations
6
medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Aug. 1, 2024
Hypertrophic cardiomyopathy (HCM) is an inherited cardiac condition affecting ~1 in 500 and exhibits marked genetic heterogeneity. Previously published 2019, 57 HCM-associated genes were curated providing the first systematic evaluation of gene-disease validity. Here we report work by ClinGen Hereditary Cardiovascular Disorders Gene Curation Expert Panel (HCVD-GCEP) to reappraise clinical validity previously new putative HCM genes. The gene curation framework was used re-classify relationships for related syndromic entities involving left ventricular hypertrophy. Genes included if their classification not definitive, time since >2-3 years. New with literature assertions initial evaluation. Existing inheritance patterns where evidence existed. Curations presented on twice monthly calls, HCVD-GCEP composed 29 individuals from 21 institutions across 6 countries. Thirty-one re-curated additional 5 potential curated. Among genes, 17 (55%) changed classification: 1 limited 4 disputed (from no known disease relationship), 9 limited), 3 definitive moderate). these, (10%) had a clinically relevant upgrade, including TNNC1, 9th sarcomere association. With evidence, two multiple (TRIM63, autosomal dominant but moderate recessive; ALPK3, strong recessive). CSRP3 semi-dominant mode (definitive). Nine (29%) downgraded disputed, further discouraging reporting variants these Five recently reported cause curated: RPS6KB1 RBM20 (limited), KLHL24 MT-TI (moderate), FHOD3 We or causation isolated LVH, sarcomere, sarcomere-associated conditions.
Language: Английский
Citations
6
Nature Genetics, Journal Year: 2024, Volume and Issue: 56(9), P. 1772 - 1779
Published: July 29, 2024
Language: Английский
Citations
4
BMC Genomics, Journal Year: 2025, Volume and Issue: 26(1)
Published: Feb. 17, 2025
Primary cardiomyopathies are major causes of heart failure, placing a substantial burden on both individuals and society. Revealing its genetic profiles can lead to better understanding the mechanism is critical for disease prevention treatment. cardiomyopathy patients were enrolled whole exome sequence was conducted analyze their profiles. Retrospective clinical information extraction analysis data implemented. A total 77 primary enrolled, comprising 65 with dilated (DCM) 12 hypertrophic (HCM). Among DCM patients, 13 variants classified as pathogenic (P) or likely (LP) identified in (18.46%), predominantly genes associated nuclear envelope sarcomere. HCM 6 P/LP discovered (50%) patients. Taking uncertain significance (VUS) into consideration, an association between number carried by characteristics revealed that more than one variant had higher proportion hyperuricemia. We map comprehensive profile Chinese population and, first time, identify possible hyperuricemia
Language: Английский
Citations
0
CARDIOVASCULAR THERAPY AND PREVENTION, Journal Year: 2025, Volume and Issue: 23(12), P. 4262 - 4262
Published: Feb. 13, 2025
Aim. To study and describe the properties of nucleotide sequence variants with incomplete penetrance associated various cardiomyopathies. Material methods . The used data genome from a previously published study. were annotated using Ensembl VEP, as well information gnomAD, ClinVar, dbNSFP databases. Results For all datasets, significant correlations (Spearman correlation coefficient -0,75 to -0,90) population frequency in gnomAD database obtained. Variants low values enriched unknown significance. Most low-penetrance missense substitutions. High-penetrance classified pathogenic, most which frameshift variants. Significant obtained weights calculated by different computational for predicting variant pathogenicity. sets, value was significantly correlated predictions four following methods: CADD, BayesDel without frequency, ClinPred. Conclusion first time, relationship type pathogenicity prediction shown.
Language: Английский
Citations
0
medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 21, 2025
Abstract Background Peripartum cardiomyopathy (PPCM) presents substantial risk of maternal mortality, but underlying cause remains unsettled. Methods We compared the prevalence dilated (DCM)-relevant genetic variants in 452 female patients (probands) African and European ancestry (AA, EA) with PPCM or DCM who had been pregnant at least once. Pathogenic likely pathogenic (P/LP) were identified DCM-associated genes. Risk partial DCM, defined as left ventricular enlargement a ejection fraction <50%, 665 FDRs probands. Results The estimated prevalences P/LP findings among 67 probands to 385 comparable within (for AA, 7.8% [95% CI: 0.0%- 15.7%] vs. 1.1%-14.4%]; for EA, 29.5% [12.5%-46.5%] 29.8% [15.5%-44.2%]). DCM/partial was not lower relative (HR, 0.77; 95% CI, 0.47 – 1.28). For an FDR non-Hispanic EA proband PPCM, lowest by age 80 26.8% (95% 15.0%-45.0%) 33.2% 21.2%-49.5%) DCM. Further validating using set genes common between studies, (26.6%; 12.6%- 40.6%) higher than general population estimate from UK Biobank study (0.6%), Also, lowest-risk (7.0% 0%-14.1%] females, 9.0% 1.6%-16.3%] males) estimates another (0.30% 0.63% males). Conclusions Comparing women those similar DCM-relevant their first-degree relatives observed. These findings, along comparisons showing FDRs, strengthen evidence basis underscore need clinical evaluations patients. Clinical Trial clinicaltrials.gov, NCT03037632 Perspective What is new? This first use familial risk, shown phenotypes (FDRs) gain insight into genetics PPCM. rare diagnosed groups. In ancestry, estimate. phenotype population-based are implications? this strengthens that DCM-related key factor A evaluation indicated following established guidelines case men
Language: Английский
Citations
0
Circulation Genomic and Precision Medicine, Journal Year: 2025, Volume and Issue: unknown
Published: March 28, 2025
In recent years, there has been a considerable influx of publications assessing the penetrance pathogenic variants associated with monogenic diseases dominant inheritance. As large and diverse groups have sequenced, it become clear that incomplete is common to most hereditary diseases, as numerous molecular, genetic, or environmental factors can cause clinical diversity among carriers same variant. this review, we discuss some these focus on existing approaches estimating penetrance, depending data available their application different sets. We also list currently large-scale sets estimates.
Language: Английский
Citations
0
Circulation, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 3, 2025
BACKGROUND: Dilated cardiomyopathy (DCM) appears to be diagnosed twice as often in male than female patients. This could attributed underdiagnosis patients or sex differences susceptibility. Up 30% of cases have an autosomal dominant monogenic cause, where equal prevalence would expected. The aim this systematic review, meta-analysis, and population study was assess the ratio with DCM, stratified by genetic status, evaluate whether is influenced diagnostic bias. METHODS: A literature search identified DCM patient cohorts discernible ratios. Exclusion criteria were studies a small (n<100), pediatric, peripartum population. Meta-analysis metaregression compared proportion participants for overall cohort following subtypes: all individual selected genes ( TTN LMNA ), gene-elusive DCM. Population ratios generated from codes also those sex-specific means using UK Biobank imaging cohort; established International Classification Diseases, 10th revision–coded, novel imaging–first, genotype-first–determined RESULTS: total 99 studies, 37 525 participants, included. had 0.30 (95% CI, 0.28–0.32), corresponding male:female (M:F) 2.38:1. similar variant (0.31 [95% 0.26–0.36]; M:F 2.22:1; P =0.56). There no significant difference when (0.30 0.24–0.37]; 2.29:1; =0.81). Furthermore, within gene variants not significantly different (0.28 0.22–0.36]; 2.51:1; =0.82) (0.35 0.27–0.44]; 1.84:1; =0.41). Overall, people disease all-cause group (0.34 0.28–0.40]; 1.98:1; =0.19). In (n=47 549), defined revision, coding 4.5:1 M:F. However, implementing imaging-first genotype-first approaches changed 1.7:1 2.3:1, respectively. CONCLUSIONS: demonstrates that prevalent partially mitigated criteria. persistent excess genotype-positive equally risk suggests additional environmental drivers sex-biased penetrance. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero ; Unique identifier: CRD42023451944.
Language: Английский
Citations
0
Cardiology in the Young, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 8
Published: Feb. 6, 2025
Abstract Dilated cardiomyopathy (DCM) is a leading cause of heart failure and the most common indication for transplant. Guidelines are regularly based on studies adults applied to young. Children adolescents diagnosed with DCM face different lifestyle challenges from individuals in adulthood that include medical trauma influenced by maturity levels confidence advocacy adults. Using UK patient-scientist’s perspective, we reviewed age-specific faced young DCM, evaluated current guidelines evidence, identified areas requiring further recommendations research. We highlight importance (i) transition clinic paediatric adult services, (ii) repeated signposting mental health (iii) standardised guidance physical activity, (iv) caution surrounding alcohol smoking, (v) dangers illegal drugs, (vi) reproductive options health. Further research needed address many uncertainties these respect age, particularly such would be welcomed who must come terms being more limited amongst healthy peers.
Language: Английский
Citations
0