Purpose: Exome sequencing (ES) could detect pathogenic variants that are unrelated to the test indication, including findings that may have an impact for patients considering conception/reproduction (reproduction-related findings [RRFs]), deliberately searched secondary findings (SFs), and incidental findings (IFs). We aimed to examine the detection rate of clinically actionable findings and to present counseling dilemmas in 840 parents of probands undergoing clinical trio ES testing.
Methods: RRFs/IFs/SFs were actively searched for in the parents as part of ES data analysis. Variants were filtered by frequency, mode of inheritance, ClinVar classification, presence in local pathogenic variant databases, and protein-truncating effect.
Results: In 14 of 420 families (3.3%), 15 RRFs were detected. Shared parental heterozygous status for autosomal recessive disorders was identified in 23.3% of consanguineous and 1.8% of nonconsanguineous couples. SFs were found in 22 of 840 individuals (2.6%), including 15 variants (7 founder variants) in cancer-predisposing genes and 4 in cardiac disease-related genes. IFs were found in 3 individuals without reported symptoms. Overall, variants of potential medical importance were detected in 9.3% of families. Challenges related to the decision whether to report variants included unreported parental phenotype, presymptomatic testing, variable disease expressivity, potential medical implications for children who are already born, and medicolegal aspects.
Conclusion: Active search for RRFs, IFs, and SFs yields a high rate of findings, which may contribute to individual medical care in parents of probands undergoing ES. A structured approach to overcome the challenges associated with reporting these findings should be considered before such an active search can be broadly adopted in clinical genomic data analysis.
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http://dx.doi.org/10.1016/j.gimo.2023.100813 | DOI Listing |
J Egypt Natl Canc Inst
December 2024
Department of Clinical Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
Background: Lung cancer is a form of cancer that is responsible for the largest incidence of deaths attributed to cancer worldwide. Non-small cell lung cancer (NSCLC) is the most prevalent of all the subtypes of the disease. Treatment with tyrosine kinase inhibitors (TKI) may help some people who have been diagnosed with non-small cell lung cancer.
View Article and Find Full Text PDFMetabolism
December 2024
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:
Background: Delineating the shared genetic architecture of type 2 diabetes with muscle mass and function and frailty is essential for unraveling the common etiology and developing holistic therapeutic strategies for these co-existing conditions.
Methods: In this genome-wide pleiotropic association study, we performed multi-level pairwise trait pleiotropic analyses using genome-wide association study summary statistics from up to 461,026 European ancestry individuals to dissect the shared genetic factors and causal relationships of type 2 diabetes and seven glycemic traits with four muscle mass- and function-related phenotypes and the frailty index.
Results: We first identified 27 pairs with significant genetic correlations through the linkage disequilibrium score regression and high-definition likelihood analysis.
Transl Oncol
December 2024
Saint Camillus International University of Medical and Health Sciences, Rome, Italy; Direzione Scientifica Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.
Background: Circulating tumor DNA (ctDNA) revolutionized the molecular diagnostics of lung cancer by enabling non-invasive, sensitive identification of actionable mutations. However, ctDNA analysis may be challenging due to tumor shedding variability, leading to false negative results. This study aims to understand the determinants for ctDNA shedding based on clinical characteristics of lung cancer patients, for a better interpretation of false negative results to be considered when ordering ctDNA analysis for clinical practice.
View Article and Find Full Text PDFLancet Digit Health
December 2024
Infectious Disease Epidemiology and Dynamics, London School of Hygiene and Tropical Medicine, London, UK.
Since the COVID-19 pandemic, considerable advances have been made to improve epidemic preparedness by accelerating diagnostics, therapeutics, and vaccine development. However, we argue that it is crucial to make equivalent efforts in the field of outbreak analytics to help ensure reliable, evidence-based decision making. To explore the challenges and key priorities in the field of outbreak analytics, the Epiverse-TRACE initiative brought together a multidisciplinary group of experts, including field epidemiologists, data scientists, academics, and software engineers from public health institutions across multiple countries.
View Article and Find Full Text PDFJ Card Fail
December 2024
School of Nursing, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Background Delivering care that is responsive to who or what is most important to patients and family caregivers is a key aspect of quality care, yet it remains unclear how clinicians can best support individuals in expressing their personal values. We aimed to describe patient- and family caregiver-identified facilitators and barriers to engaging in values discussions with clinicians following implantation of a left ventricular assist device (LVAD). Methods and results Using a qualitative descriptive approach, patients with an LVAD and their caregivers participated in one-on-one semi structured interviews and self-reported sociodemographics (January 2023-July 2023).
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