Genetic Testing for Rare Genetic Disorders

(GIVE Trial)

Overseen By Seema Lalani, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Disqualifiers: Known genetic diseases

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist children with rare genetic disorders living along the Texas-Mexico border. Researchers use whole genome sequencing (WGS) to examine a person's entire DNA for clues about their condition. The trial aims to enhance care for these children by employing a special online model called Consultagene for remote evaluations. Children residing in the Rio Grande Valley or El Paso, Texas, with an undiagnosed rare genetic disease may be suitable candidates for this trial. As an unphased trial, it provides families with a unique opportunity to access advanced genetic evaluations and potentially improve their child's care.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What prior data suggests that whole genome sequencing is safe for children with rare genetic disorders?

Research has shown that whole genome sequencing (WGS) is generally safe and is increasingly used to diagnose rare genetic diseases. Many studies have used WGS to identify genetic conditions without major safety concerns. In these studies, WGS was well-tolerated, meaning it typically doesn't harm participants.

WGS involves reading a person's entire genetic code to detect changes that might cause disease. The process is non-invasive, requiring only a blood or saliva sample, without surgery or other potentially harmful procedures.

So far, research has not reported any harmful effects from WGS, making it a promising and safe option for diagnosing rare conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using whole genome sequencing (WGS) for diagnosing rare genetic disorders because it offers a comprehensive look at a person's entire DNA, which is something traditional genetic tests can't do. Unlike standard tests that target specific genes or regions, WGS examines every part of the genome, potentially identifying rare or unexpected mutations that might be missed otherwise. This means WGS can provide a more accurate diagnosis, leading to better understanding and management of these rare conditions.

What evidence suggests that whole genome sequencing is effective for improving genetic health in children with rare disorders?

Research has shown that whole genome sequencing (WGS), which all participants in this trial will undergo, can effectively diagnose rare genetic disorders. Studies have found a success rate of up to 24% in identifying a genetic cause in children. Nearly one in four children could receive a clear diagnosis, aiding in treatment guidance. WGS has improved patient care in up to 77% of cases, often enhancing condition management. Additionally, WGS is considered cost-effective for diagnosing genetic disorders, which is important for families seeking answers. These findings suggest that WGS could be a valuable tool for improving genetic health in underserved areas. ^{6 7 8 9 10}

Who Is on the Research Team?

Seema Lalani

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for pediatric patients living in the Rio Grande Valley, Texas, who have rare genetic diseases that remain undiagnosed. Children already diagnosed with a known genetic disease cannot participate.

Inclusion Criteria

Children who live in the Rio Grande Valley, Texas and have rare genetic conditions that have not been diagnosed yet.

Exclusion Criteria

Children with known inherited diseases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Virtual Evaluation

Participants receive virtual genetics evaluation through the Consultagene platform

4-6 weeks

Virtual visits as needed

Genomic Sequencing

Participants undergo whole genome sequencing and interpretation for rapid genetic diagnoses

4 weeks

Follow-up

Participants are monitored for health outcomes and effectiveness of genetic diagnoses

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Whole genome sequencing (WGS)

Trial Overview

The study is testing a web-based model called Consultagene to deliver care and perform Whole Genome Sequencing (WGS) remotely to help identify genetic disorders in children from less resourced areas.

How Is the Trial Designed?

Group I: WGS arm Experimental Treatment 1 Intervention

All 200 patients recruited will undergo WGS

Whole genome sequencing (WGS) is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Whole Genome Sequencing for:

• Rare genetic disorders
• Congenital anomalies
• Neurodevelopmental disorders

Approved in United States as Whole Genome Sequencing for:

• Unexplained congenital anomalies
• Neurodevelopmental disorders
• Intellectual disability
• Developmental delay

Approved in United Kingdom as Whole Genome Sequencing for:

• Rare genetic disorders
• Congenital anomalies
• Neurodevelopmental disorders
• Cancer

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Published Research Related to This Trial

Whole-genome sequencing (WGS) has become much faster and cheaper, making it a promising tool for early diagnosis of rare genetic disorders, which affect 3%-5% of newborns.

Despite the potential of WGS to improve diagnosis and treatment, challenges remain in drug development and regulatory approval that hinder the transition to effective therapies for these disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole-genome sequencing holds the key to the success of gene-targeted therapies. Vockley, J., Aartsma-Rus, A., Cohen, JL., et al.[2023]

A comprehensive whole-genome sequencing (WGS) pipeline for diagnosing genetic disorders was developed and validated using 45 samples with known variants, demonstrating its effectiveness in detecting various genetic alterations.

The pipeline includes advanced bioinformatics tools for identifying multiple types of genetic variants, ensuring a robust approach to genetic testing that can improve clinical diagnostics for genetic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Test development, optimization and validation of a WGS pipeline for genetic disorders. Yang, Z., Yang, X., Sun, Y., et al.[2023]

Whole genome sequencing (WGS) identified pathogenic or likely pathogenic variants in 20% of families with hypertrophic cardiomyopathy (HCM) where previous genetic tests were inconclusive, revealing new genetic causes not detected by standard testing methods.

As a first-line genetic test, WGS was able to find pathogenic variants in 42% of families that had never undergone genetic testing before, demonstrating its effectiveness in diagnosing HCM and improving management for affected families.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole Genome Sequencing Improves Outcomes of Genetic Testing in Patients With Hypertrophic Cardiomyopathy. Bagnall, RD., Ingles, J., Dinger, ME., et al.[2019]

Whole genome sequencing (WGS) is emerging as a promising first-tier diagnostic tool for identifying rare genetic disorders, but there is a need for standardized practices to ensure its effectiveness.

The Medical Genome Initiative has developed best practice recommendations for interpreting and reporting clinical WGS results, aiming to improve access and quality of this diagnostic test in healthcare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Best practices for the interpretation and reporting of clinical whole genome sequencing. Austin-Tse, CA., Jobanputra, V., Perry, DL., et al.[2022]

Whole-genome sequencing (WGS) significantly improved clinical management for acutely ill infants, with 21.1% of those receiving early results experiencing a change in management compared to only 10.3% in the delayed group, indicating a strong effect on treatment decisions.

The study involved 354 infants and showed that WGS not only provided a molecular diagnosis for more patients (31.0% in the early group vs 15.0% in the delayed group) but also has the potential to reduce healthcare disparities by offering equitable diagnostic access.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Whole-Genome Sequencing on the Clinical Management of Acutely Ill Infants With Suspected Genetic Disease: A Randomized Clinical Trial. Krantz, ID., Medne, L., Weatherly, JM., et al.[2022]

Whole-genome sequencing (WGS) is a powerful tool for diagnosing hereditary disorders, especially for patients with undiagnosed conditions, potentially ending their diagnostic journey and improving clinical care.

The clinical WGS test provides high-quality sequencing data and detailed reports that include both primary results and optional secondary findings, allowing for personalized patient care and informed decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting of Clinical Genome Sequencing Results. Song, C., Duzkale, H., Shen, J.[2023]

In a pilot program at Children's Hospital of Wisconsin, whole genome sequencing (WGS) was used to diagnose genetic disorders in 22 patients, achieving an initial diagnosis rate of 14%, which increased to 36% after reanalysis.

In 75% of the diagnosed cases, the identified genetic variants influenced treatment decisions or medical monitoring, highlighting the practical impact of WGS in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Application of Whole Genome Sequencing in a Medical Genetics Clinic. Bick, D., Fraser, PC., Gutzeit, MF., et al.[2020]

Whole genome sequencing (WGS) significantly improves the diagnostic yield for suspected genetic disorders in pediatric patients, achieving a 38.6% success rate compared to 37.8% for whole exome sequencing (WES) and only 7.8% for usual care.

The study indicates that WGS is particularly effective for diagnosing Mendelian diseases, suggesting it may be a superior option for targeted genetic diagnosis in children with severe disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole genome sequencing diagnostic yield for paediatric patients with suspected genetic disorders: systematic review, meta-analysis, and GRADE assessment. Nurchis, MC., Altamura, G., Riccardi, MT., et al.[2023]

Whole genome sequencing (WGS) successfully diagnosed a 7-year-old girl with a severe undiagnosed panvascular artery disease, identifying mutations in the YY1AP1 gene linked to Grange syndrome.

This case highlights the efficacy of WGS in diagnosing rare diseases, achieving a molecular diagnosis where traditional methods failed, and suggests that WGS can expand the understanding of genetic mutations associated with such conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole genome sequencing reveals a frameshift mutation and a large deletion in YY1AP1 in a girl with a panvascular artery disease. Raggio, V., Dell'Oca, N., Simoes, C., et al.[2022]

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