scholarly journals The case for early use of rapid whole-genome sequencing in management of critically ill infants: late diagnosis of Coffin–Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease, and recurrent infections

2018 ◽  
Vol 4 (3) ◽  
pp. a002469 ◽  
Author(s):  
Nathaly M. Sweeney ◽  
Shareef A. Nahas ◽  
Shimul Chowdhury ◽  
Miguel Del Campo ◽  
Marilyn C. Jones ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Diaphragmatic Hernia ◽  
Whole Genome Sequencing ◽  
Critically Ill ◽  
Genome Sequencing ◽  
Congenital Heart ◽  
Whole Genome ◽  
Recurrent Infections ◽  
Early Use

scholarly journals Rapid whole genome sequencing impacts care and resource utilization in infants with congenital heart disease

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Nathaly M. Sweeney ◽  
Shareef A. Nahas ◽  
Sh. Chowdhury ◽  
Sergey Batalov ◽  
Michelle Clark ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genetic Disease ◽  
Congenital Heart ◽  
Cost Of Care ◽  
Morbidity And Mortality ◽  
Whole Genome ◽  
Microarray Gene

AbstractCongenital heart disease (CHD) is the most common congenital anomaly and a major cause of infant morbidity and mortality. While morbidity and mortality are highest in infants with underlying genetic conditions, molecular diagnoses are ascertained in only ~20% of cases using widely adopted genetic tests. Furthermore, cost of care for children and adults with CHD has increased dramatically. Rapid whole genome sequencing (rWGS) of newborns in intensive care units with suspected genetic diseases has been associated with increased rate of diagnosis and a net reduction in cost of care. In this study, we explored whether the clinical utility of rWGS extends to critically ill infants with structural CHD through a retrospective review of rWGS study data obtained from inpatient infants < 1 year with structural CHD at a regional children’s hospital. rWGS diagnosed genetic disease in 46% of the enrolled infants. Moreover, genetic disease was identified five times more frequently with rWGS than microarray ± gene panel testing in 21 of these infants (rWGS diagnosed 43% versus 10% with microarray ± gene panels, p = 0.02). Molecular diagnoses ranged from syndromes affecting multiple organ systems to disorders limited to the cardiovascular system. The average daily hospital spending was lower in the time period post blood collection for rWGS compared to prior (p = 0.003) and further decreased after rWGS results (p = 0.000). The cost was not prohibitive to rWGS implementation in the care of this cohort of infants. rWGS provided timely actionable information that impacted care and there was evidence of decreased hospital spending around rWGS implementation.

scholarly journals Publisher Correction: Rapid whole genome sequencing impacts care and resource utilization in infants with congenital heart disease

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Nathaly M. Sweeney ◽  
Shareef A. Nahas ◽  
Shimul Chowdhury ◽  
Sergey Batalov ◽  
Michelle Clark ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Whole Genome Sequencing ◽  
Resource Utilization ◽  
Genome Sequencing ◽  
Congenital Heart ◽  
Whole Genome

scholarly journals Author Correction: Rapid whole genome sequencing impacts care and resource utilization in infants with congenital heart disease

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Nathaly M. Sweeney ◽  
Shareef A. Nahas ◽  
Shimul Chowdhury ◽  
Sergey Batalov ◽  
Michelle Clark ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Whole Genome Sequencing ◽  
Resource Utilization ◽  
Genome Sequencing ◽  
Congenital Heart ◽  
Whole Genome

scholarly journals Factors Affecting Consent Rate for Whole Genome Sequencing of Patients with Congenital Heart Disease

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Jinny Tsang
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Congenital Heart ◽  
Minority Groups ◽  
Heart Diseases ◽  
Whole Genome ◽  
Consent Rate ◽  
Sequencing Project

The Whole Genome Sequencing Project initiated by The Hospital for Sick Children of Toronto intents to enroll patients between one to eighteen years of age with congenital heart disease to test the efficiency of such a method for potential personalized diagnoses and treatments. Twenty-five randomly approached patients were chosen to be observed of their consent rate to the project based on factors of age, gender, ethnicity, presence of heart diseases in the patient’s family, and type of congenital heart disease represented. Females and ethnicities not of European descent are considered to be a part of the minority groups, generally being under represented thus having a lower consent rate. There were no significant correlations between consent rates and familial history of heart disease, type of heart disease and age groups. All these findings can aid in future studies of the SickKids Hospital; which patients should be approached for higher consent rates, and the inclusivity of minority groups to alleviate bias in medical studies.

scholarly journals Decoding Genetics of Congenital Heart Disease Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs)

2021 ◽  
Vol 9 ◽  
Author(s):  
Hui Lin ◽  
Kim L. McBride ◽  
Vidu Garg ◽  
Ming-Tao Zhao
Keyword(s):  
Stem Cells ◽  
Congenital Heart Disease ◽  
Heart Disease ◽  
Induced Pluripotent Stem Cells ◽  
Genome Sequencing ◽  
Pluripotent Stem Cells ◽  
Congenital Heart ◽  
Model Systems ◽  
Patient Specific ◽  
Induced Pluripotent

Congenital heart disease (CHD) is the most common cause of infant death associated with birth defects. Recent next-generation genome sequencing has uncovered novel genetic etiologies of CHD, from inherited and de novo variants to non-coding genetic variants. The next phase of understanding the genetic contributors of CHD will be the functional illustration and validation of this genome sequencing data in cellular and animal model systems. Human induced pluripotent stem cells (iPSCs) have opened up new horizons to investigate genetic mechanisms of CHD using clinically relevant and patient-specific cardiac cells such as cardiomyocytes, endothelial/endocardial cells, cardiac fibroblasts and vascular smooth muscle cells. Using cutting-edge CRISPR/Cas9 genome editing tools, a given genetic variant can be corrected in diseased iPSCs and introduced to healthy iPSCs to define the pathogenicity of the variant and molecular basis of CHD. In this review, we discuss the recent progress in genetics of CHD deciphered by large-scale genome sequencing and explore how genome-edited patient iPSCs are poised to decode the genetic etiologies of CHD by coupling with single-cell genomics and organoid technologies.

Coming up to Speed on Whole Genome Sequencing in Critically Ill Children

2018 ◽  
Vol 1 (1) ◽  
pp. 1-8
Author(s):  
Isabelle Thiffault ◽  
Emily Farrow ◽  
Maxime Cadieux-Dion ◽  
Carol J. Saunders
Keyword(s):  
Whole Genome Sequencing ◽  
Critically Ill ◽  
Genome Sequencing ◽  
Critically Ill Children ◽  
Whole Genome

scholarly journals Whole-genome sequencing for identification of Mendelian disorders in critically ill infants: a retrospective analysis of diagnostic and clinical findings

2015 ◽  
Vol 3 (5) ◽  
pp. 377-387 ◽  
Author(s):  
Laurel K Willig ◽  
Josh E Petrikin ◽  
Laurie D Smith ◽  
Carol J Saunders ◽  
Isabelle Thiffault ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Retrospective Analysis ◽  
Critically Ill ◽  
Genome Sequencing ◽  
Clinical Findings ◽  
Whole Genome ◽  
Mendelian Disorders

scholarly journals Whole genome sequencing identifies multiple loci for critical illness caused by COVID-19

2021 ◽  
Author(s):  
Athanasios Kousathanas ◽  
Erola Pairo-Castineira ◽  
Konrad Rawlik ◽  
Alex Stuckey ◽  
Christopher A Odhams ◽  
...  
Keyword(s):  
Critical Care ◽  
Critical Illness ◽  
Whole Genome Sequencing ◽  
Critically Ill ◽  
Genome Sequencing ◽  
Blood Type ◽  
Host Immune System ◽  
Whole Genome ◽  
Mucin Expression ◽  
Population Controls

Critical illness in COVID-19 is caused by inflammatory lung injury, mediated by the host immune system. We and others have shown that host genetic variation influences the development of illness requiring critical care or hospitalisation following SARS-Co-V2 infection. The GenOMICC (Genetics of Mortality in Critical Care) study is designed to compare genetic variants in critically-ill cases with population controls in order to find underlying disease mechanisms. Here, we use whole genome sequencing and statistical fine mapping in 7,491 critically-ill cases compared with 48,400 population controls to discover and replicate 22 independent variants that significantly predispose to life-threatening COVID-19. We identified 15 new independent associations with severe COVID-19, including variants within genes involved in interferon signalling (IL10RB, PLSCR1), leucocyte differentiation (BCL11A), and blood type secretor status (FUT2). Using transcriptome-wide association and colocalisation to infer the effect of gene expression on disease severity, we find evidence implicating expression of multiple genes, including reduced expression of a membrane flippase (ATP11A), and increased mucin expression (MUC1), in severe disease. We show that comparison between critically-ill cases and population controls is highly efficient for genetic association analysis and enables detection of therapeutically-relevant mechanisms of disease. Therapeutic predictions arising from these findings require testing in clinical trials.

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