Genome Sequencing for Congenital Heart Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Scripps Translational Science Institute
Disqualifiers: Gestational age 38 weeks, Chromosomal abnormality, Under 18, others
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This study is enrolling pregnant persons treated at Rady Children's Hospital fetal cardiology program with a prenatal diagnosis of congenital heart disease to look for genetic disorders in the fetus or unborn baby.
Congenital heart disease (CHD) is a group of structural differences to the heart that represent the most common birth defect among liveborn infants world-wide. CHD is the leading cause of birth-defect associated infant death. Prenatal detection allows for delivery planning, postnatal repair, specialized medications, and detailed counseling for parents. Up to one in three fetuses with CHD may have a genetic cause. In babies, knowing about genetic diseases helps patients and doctors provide the best care for their babies. If identified prenatally, this same knowledge may help participants prepare for their location of delivery, meet with specialists, and consider specialized treatments and medications that may be appropriate.
The diagnostic yield and clinical utility of whole genome sequencing (WGS) in fetuses with prenatally detected congenital heart disease (CHD) will be compared to routine clinical testing in patients choosing amniocentesis or chorionic villus sampling. DNA will be obtained from fetal samples and biological parent blood samples and analyzed according to standard clinical interpretation guidelines. Results will be reported to healthcare providers and patients and measures of clinical utility will be collected. Additionally, measures of stress, anxiety, depression, and perceived utility of information will be assessed by validated survey tools. A historical cohort of patients electing for diagnostic procedures will be used as a comparison population.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications.
What data supports the effectiveness of the treatment Whole Genome Sequencing for Congenital Heart Disease?
Rapid whole genome sequencing (rWGS) has been shown to increase the rate of diagnosis and reduce the cost of care in newborns with suspected genetic diseases, including those with congenital heart disease. This suggests that using rWGS can help identify genetic causes of heart defects more quickly, potentially leading to better management and outcomes for affected infants.
12345Is genome sequencing safe for humans?
Genome sequencing, including whole genome sequencing (WGS) and next-generation sequencing (NGS), has been used in various studies and is generally considered safe for humans. These technologies have been applied in different medical conditions, including congenital heart disease, without specific safety concerns reported in the research.
12356How is whole genome sequencing different from other treatments for congenital heart disease?
Whole genome sequencing (WGS) is unique because it analyzes the entire genetic makeup to identify potential genetic causes of congenital heart disease, which can lead to more accurate diagnoses and personalized treatment plans. Unlike traditional methods, WGS can uncover rare genetic variants that might not be detected otherwise, potentially reducing the cost of care and improving outcomes for patients.
12378Eligibility Criteria
This trial is for pregnant individuals with a prenatal diagnosis of congenital heart disease in their fetus, who want genetic testing and are planning to undergo amniocentesis or chorionic villus sampling.Inclusion Criteria
I am pregnant and my unborn baby has been diagnosed with a heart defect.
I want genetic testing and plan to have amniocentesis or CVS.
Exclusion Criteria
Gestational age of 38 weeks or greater
My condition is fully explained by a genetic diagnosis.
I am pregnant and under 18.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Whole Genome Sequencing
Whole genome sequencing (WGS) is performed on fetuses with prenatally detected congenital heart disease (CHD) to assess diagnostic yield and effect of prenatal versus postnatal phenotype on diagnostic yield.
Duration of enrollment
Consultation and Planning
Participants receive consultation with subspecialist providers to plan delivery location and postnatal interventions based on WGS results.
Throughout pregnancy
Follow-up
Participants are monitored for psychological impact and clinical utility of WGS results, including measures of stress, anxiety, and depression.
18 months after birth
Participant Groups
The study tests whole genome sequencing on fetal samples from pregnancies affected by congenital heart disease. It aims to compare the effectiveness of this method with routine clinical testing for detecting genetic disorders.
1Treatment groups
Experimental Treatment
Group I: Whole Genome Sequencing (WGC) from subject samplesExperimental Treatment1 Intervention
Whole Genome Sequencing is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Whole Genome Sequencing for:
- Genetic disorders
- Congenital heart disease
- Prenatal diagnosis
🇪🇺 Approved in European Union as Whole Genome Sequencing for:
- Genetic disorders
- Congenital heart disease
- Rare genetic conditions
🇨🇦 Approved in Canada as Whole Genome Sequencing for:
- Genetic disorders
- Congenital heart disease
- Prenatal diagnosis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Rady Children's Institute for Genomic MedicineSan Diego, CA
Loading ...
Who Is Running the Clinical Trial?
Scripps Translational Science InstituteLead Sponsor
References
Rapid whole genome sequencing impacts care and resource utilization in infants with congenital heart disease. [2023]Congenital 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
Clinical application of targeted next-generation sequencing in fetuses with congenital heart defect. [2018]To assess the value of targeted next-generation sequencing (NGS) in prenatal diagnosis of congenital heart defects (CHD) and to investigate the genetic etiology of prenatal CHD.
Application of high-throughput sequencing for studying genomic variations in congenital heart disease. [2014]Congenital heart diseases (CHD) represent the most common birth defect in human. The majority of cases are caused by a combination of complex genetic alterations and environmental influences. In the past, many disease-causing mutations have been identified; however, there is still a large proportion of cardiac malformations with unknown precise origin. High-throughput sequencing technologies established during the last years offer novel opportunities to further study the genetic background underlying the disease. In this review, we provide a roadmap for designing and analyzing high-throughput sequencing studies focused on CHD, but also with general applicability to other complex diseases. The three main next-generation sequencing (NGS) platforms including their particular advantages and disadvantages are presented. To identify potentially disease-related genomic variations and genes, different filtering steps and gene prioritization strategies are discussed. In addition, available control datasets based on NGS are summarized. Finally, we provide an overview of current studies already using NGS technologies and showing that these techniques will help to further unravel the complex genetics underlying CHD.
Effect of Whole-Genome Sequencing on the Clinical Management of Acutely Ill Infants With Suspected Genetic Disease: A Randomized Clinical Trial. [2022]Whole-genome sequencing (WGS) shows promise as a first-line genetic test for acutely ill infants, but widespread adoption and implementation requires evidence of an effect on clinical management.
Moving Genomics to Routine Care: An Initial Pilot in Acute Cardiovascular Disease. [2021]Whole-genome sequencing (WGS) costs are falling, yet, outside oncology, this information is seldom used in adult clinics. We piloted a rapid WGS (rWGS) workflow, focusing initially on estimating power for a feasibility study of introducing genome information into acute cardiovascular care.
Diagnostic yield of whole exome data in fetuses aborted for conotruncal malformations. [2022]We investigated a custom congenital heart disease (CHD) geneset to assess the diagnostic value of whole-exome sequencing (WES) in karyotype- and copy number variation (CNV)-negative aborted fetuses with conotruncal defects (CTDs), and to explore the impact of postnatal phenotyping on genetic diagnosis.
Targeted Next-Generation Sequencing in Patients with Non-syndromic Congenital Heart Disease. [2018]Congenital heart disease (CHD) is a genetically heterogeneous disease. Targeted next-generation sequencing (NGS) offers a unique opportunity to sequence multiple genes at lower cost and effort compared to Sanger sequencing. We tested a targeted NGS of a specific gene panel in a relatively large population of non-syndromic CHD patients. The patient cohort comprised 68 CHD patients (45 males; 8.3 ± 1.7 years). Amplicon libraries for 16 CHD-strictly related genes were generated using a TruSeq® Custom Amplicon kit (Illumina, CA) and sequenced using the Illumina MiSeq platform. Sequence data were processed through the MiSeq Reporter and wANNOVAR softwares. After applying stringent filtering criteria, 20 missense variants in 9 genes were predicted to be damaging and were validated by Sanger sequencing with 100% concordance. Fourteen variants were present in public databases with very rare allele frequency, of which four variants (p.Arg25Cys in NKX2-5, p.Val763Ile in ZFPM2, p.Arg1398Gln and Gly1826Asp in MYH6) have been previously linked to CHD or cardiomyopathy. The remaining six variants in four genes (GATA4, NKX2-5, NOTCH1, TBX1) were novel mutations, currently not found in public databases, and absent in 200 control alleles of healthy subjects. Four patients (5.8%) carried two missense variants (1 compound heterozygote in the same gene and 3 double heterozygotes in different genes), with possibly synergistic deleterious effects. Targeted NGS is a powerful and efficient tool to detect DNA sequence variants in multiple genes, providing the opportunity for discovery of the co-occurrence of two or more missense rare variants.
Identification of clinically actionable variants from genome sequencing of families with congenital heart disease. [2022]Congenital heart disease (CHD) affects up to 1% of live births. However, a genetic diagnosis is not made in most cases. The purpose of this study was to assess the outcomes of genome sequencing (GS) of a heterogeneous cohort of CHD patients.