Validation of Optical Genome Mapping for the Identification of Constitutional Genomic Variants in a Postnatal Cohort
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| ClinicalTrials.gov Identifier: NCT05295277 |
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Recruitment Status :
Recruiting
First Posted : March 25, 2022
Last Update Posted : March 25, 2022
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| Condition or disease | Intervention/treatment |
|---|---|
| Developmental Disability Intellectual Disability Autism Spectrum Disorder Congenital Anomaly Fragile X Syndrome Facioscapulohumeral Muscular Dystrophy 1 | Other: Standard of care genetic testing group |
Optical genome mapping (OGM) is an emerging next-generation cytogenomic tool that enables a comprehensive analysis of structural variants (SVs) in the genome. OGM, in its current iteration, is performed on the Saphyr system, which is developed and marketed by Bionano Genomics (San Diego, CA). OGM employs imaging of ultra-long DNA molecules (>150 kbp) that are labeled at a unique 6 base-pair sequence motif (CTTAAG) that occurs throughout the genome. The images of the labeled DNA molecules are used to generate a de novo assembly that can be compared to a reference genome to identify all classes of SVs, such as deletions, duplications, balanced/ unbalanced genomic rearrangements (insertions, inversions, and translocations), and repeat array expansions/contractions). In addition, a separate coverage-based algorithm enables the detection of genome-wide copy number analysis (similar to CMA), and the absence of heterozygosity (AOH) analysis. In the same assay, a concurrent or stepwise data analysis pipeline allows for sizing pathogenic CGG repeat expansions (consistent with fragile X syndrome) as well as D4Z4 repeat contractions which are consistent with facioscapulohumeral muscular dystrophy type 1 (FSHD1). Recently, in several studies, OGM has demonstrated excellent concordance with standard-of-care testing. Importantly, the OGM workflow can provide results within three-five days.
The aim of this double-blinded, multi-site, retrospective, observational, Institutional Review Board (IRB)-approved study is to evaluate the concordance of structural variant detection by OGM compared to standard of care tests (such as CMA, karyotyping, Southern blot analysis, PCR, FISH, and/or NGS, etc.), in a large cohort containing a variety of SVs including aneuploidies, intragenic and contiguous deletions, duplications, balanced and unbalanced translocations, inversions, isochromosomes, ring chromosomes, repeat expansions, repeat contractions, and more. This study is also designed to assess the sensitivity, specificity, and reproducibility of OGM analysis conducted at multiple sites, by numerous operators, and on different Saphyr instruments. Consensus testing and interpretation protocols were developed and implemented at all sites.
| Study Type : | Observational |
| Estimated Enrollment : | 1000 participants |
| Observational Model: | Cohort |
| Time Perspective: | Retrospective |
| Official Title: | Validation of Optical Genome Mapping for the Identification of Constitutional Genomic Variants in a Postnatal Cohort |
| Actual Study Start Date : | November 30, 2020 |
| Estimated Primary Completion Date : | March 31, 2024 |
| Estimated Study Completion Date : | June 30, 2024 |
| Group/Cohort | Intervention/treatment |
|---|---|
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Standard of care genetic testing group
Individuals with genomic test results from a standard of care (SOC) test (such as CMA, karyotyping, Southern blot analysis, PCR, FISH, and/or NGS, etc.) will be enrolled in the study to compare the SOC result to results from optical genome mapping.
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Other: Standard of care genetic testing group
N/A - no intervention as this is an observational study. |
- Sensitivity/Concordance and specificity of OGM with standard of care testing for detection of structural variants. [ Time Frame: Through study completion, an average of 1 year ]OGM results are evaluated against the standard of care test and concordance (sensitivity and specificity) will be determined.
- Reproducibility and identification of structural variants beyond the limit of detection of standard of care methods. [ Time Frame: Through study completion, an average of 1 year ]Inter-site as well as inter and intra-run variability of OGM will be assessed by reproducibility studies.
Biospecimen Retention: Samples With DNA
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
Inclusion Criteria:
- Individual with a genomic aberration identified by CMA, karyotyping, Southern blot analysis, PCR, FISH, and/or NGS or other standard of care (SOC) genetic testing technology whose clinical test results are available to compare with results from OGM.
- Patients with prior negative SOC genetic testing results whose results are available to compare with results from OGM.
Exclusion Criteria:
- Any individual who opted-out of research at the testing laboratory.
- An individual whose genetic test contains the following variants: pathogenic sequence variants, abnormalities involving acrocentric p-arms and centromeres, below 20% for mosaicism, and tetraploidy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05295277
| Contact: Alex Hastie, PhD | 267-315-0914 | ahastie@bionanogenomics.com | |
| Contact: Keith Gligorich, PhD | 801-870-9664 | kgligorich@bionanogenomics.com |
| United States, Georgia | |
| Praxis Genomics | Active, not recruiting |
| Atlanta, Georgia, United States, 30328 | |
| Augusta University Research Institute | Active, not recruiting |
| Augusta, Georgia, United States, 30912 | |
| United States, Iowa | |
| University of Iowa Hospitals & Clinics, Molecular Pathology | Active, not recruiting |
| Iowa City, Iowa, United States, 52242 | |
| United States, New York | |
| Columbia University Irving Medical Center | Active, not recruiting |
| New York, New York, United States, 10032 | |
| DNA Microarray CGH Laboratory, Department of Pathology, University of Rochester Medical Center | Active, not recruiting |
| W. Henrietta, New York, United States, 14586 | |
| United States, South Carolina | |
| Greenwood Genetic Center | Recruiting |
| Greenwood, South Carolina, United States, 29646 | |
| Principal Investigator: Steven A. Skinner, MD | |
| United States, Utah | |
| Lineagen (A Bionano Genomics Company) | Recruiting |
| Salt Lake City, Utah, United States, 84109 | |
| United States, Wisconsin | |
| Medical College of Wisconsin | Active, not recruiting |
| Milwaukee, Wisconsin, United States, 53226 | |
| Principal Investigator: | Alka Chaubey, PhD, FACMG | Bionano Genomics |
Other Publications:
| Responsible Party: | Bionano Genomics |
| ClinicalTrials.gov Identifier: | NCT05295277 |
| Other Study ID Numbers: |
20203726 |
| First Posted: | March 25, 2022 Key Record Dates |
| Last Update Posted: | March 25, 2022 |
| Last Verified: | March 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Validation study Comparison study New technology compared to standard of care |
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Muscular Dystrophies Muscular Dystrophy, Facioscapulohumeral Intellectual Disability Fragile X Syndrome Congenital Abnormalities Autism Spectrum Disorder Developmental Disabilities Child Development Disorders, Pervasive Neurodevelopmental Disorders Mental Disorders Muscular Disorders, Atrophic Muscular Diseases |
Musculoskeletal Diseases Neuromuscular Diseases Nervous System Diseases Genetic Diseases, Inborn Neurobehavioral Manifestations Neurologic Manifestations Mental Retardation, X-Linked Sex Chromosome Disorders Chromosome Disorders Genetic Diseases, X-Linked Heredodegenerative Disorders, Nervous System |