Study Using OGM in Neural Tube Defects Reveals Previously Unreported Variants and Candidate Genes with Potential Links to the Devastating Birth Defect

Rhea-AI Summary

Bionano Genomics (BNGO) and Greenwood Genetic Center published groundbreaking research in Genome Research using optical genome mapping (OGM) to study neural tube defects (NTDs). The study analyzed 104 NTD cases, revealing significant findings:

The research detected:

• Pathogenic structural variants in 8% of cases (8/104)
• Variants affecting known NTD pathway genes in 13% of cases (14/104)
• Variants affecting NTD-associated genes from mouse models in 9% of cases (9/104)

The study identified four novel candidate genes (RMND5A, HNRNPC, FOXD4, and RBBP4) potentially linked to NTDs and expanded clinical implications for AMER1 and TGIF1. With NTDs affecting approximately 300,000 births annually worldwide, this research provides new insights into genetic factors in 30% of combined cases, potentially improving future patient management and therapeutic interventions.

Positive

• Successfully detected genetic variants in 30% of combined cases, significantly higher than current methods
• Identified four new candidate genes potentially linked to NTDs
• Demonstrated superior detection capabilities compared to traditional methods (8% vs 6%)

Negative

• None.

Insights

Genomics Research Specialist

This research publication represents a significant advancement in understanding neural tube defects (NTDs) through optical genome mapping (OGM) technology. The study's findings are scientifically notable for several reasons:

The detection rate of pathogenic structural variants in 8% of cases demonstrates that OGM matches or slightly exceeds the combined success rate of conventional methods (karyotyping and chromosomal microarray) in identifying genetic factors behind NTDs. More importantly, OGM identified variants affecting genes in known NTD pathways in an additional 13% of cases, plus variants in mouse-model NTD genes in another 9%.

What's particularly valuable is the discovery of novel NTD candidate genes (RMND5A, HNRNPC, FOXD4, RBBP4) and expanded clinical implications for known genes (AMER1, TGIF1). This significantly broadens our understanding of NTD genetics, potentially explaining nearly 30% of cases compared to just 8% with current methods.

The scale of the problem—300,000 births affected annually worldwide—underscores the clinical importance. Despite folic acid supplementation reducing incidence, NTDs remain devastating birth defects with significant knowledge gaps. This study demonstrates OGM's utility in detecting structural variants that other technologies miss, particularly in a complex polygenic condition where comprehensive genomic analysis is crucial.

Healthcare Investment Analyst

This publication represents meaningful scientific validation for Bionano's optical genome mapping (OGM) technology in a clinically relevant application. The study demonstrates OGM's potential to identify genetic factors in neural tube defects at rates comparable to or better than existing methods, with additional capabilities for discovering novel variants.

For Bionano, this adds to the growing body of evidence supporting OGM's utility in genetic disease research—an important milestone for a company working to expand its technology's adoption. The research demonstrates OGM's complementary role alongside existing methods like karyotyping, chromosomal microarray, and next-generation sequencing, potentially positioning it as a valuable additional tool in comprehensive genetic analysis.

With NTDs affecting approximately 300,000 births annually, there's substantial clinical need for improved genetic diagnostics in this area. The study showed pathogenic or likely pathogenic findings in 21% of cases (8% confirmed pathogenic plus 13% likely pathogenic), with additional candidate genes in 9% of cases.

While this research publication alone doesn't guarantee immediate clinical adoption or revenue growth, it establishes OGM as a valuable research tool for discovering genetic factors in birth defects. For Bionano, building this scientific evidence base is crucial for long-term technology adoption in both research and eventual clinical applications.

SAN DIEGO, and GREENWOOD, S.C., March 24, 2025 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) and Greenwood Genetic Center (GGC) today announced a publication in Genome Research describing the first study to use optical genome mapping (OGM) to investigate the genetic landscape of neural tube defects (NTDs). NTDs are the most common birth defect of the central nervous system and some of the most devastating congenital conditions. Despite an expected genetic link in as many as 60-70% of cases, methods currently in use, including karyotyping (KT), chromosomal microarray (CMA) and next-generation sequencing (NGS), collectively identify pathogenic gene variants in only about 8% of cases, suggesting more work is needed to better understand the underlying genetic drivers of NTDs.

In this GGC study, OGM was used to provide a comprehensive, genome-wide analysis of structural variants (SVs) across a study cohort of 104 NTD cases. The key findings include:

• Detection of SVs with known pathogenic significance in 8% (8/104) of cases, compared to a combined success rate of approximately 6% in NTDs for KT and CMA and consistent with what is typically described in research studies for the combination of KT, CMA and NGS applied to this condition

• Detection of SVs that affected genes known to be part of NTD pathways in 13% (14/104) of cases, which would be considered likely pathogenic given their association with known NTD pathways

• Detection of SVs that affected genes associated with NTDs in mouse models in 9% (9/104) of cases, which require additional investigation to establish a link to NTDs in human, but represent promising candidates that were previously unreported
  
• Discovery of novel NTD candidate genes and expansion of clinical implications of others, with identification of four genes – RMND5A, HNRNPC, FOXD4, and RBBP4 – having strong potential involvement in NTDs, and add NTD risk to the known clinical implications of AMER1 and TGIF1

Neural tube defects impact approximately 300,000 births annually worldwide and remain a leading cause of infant mortality and lifelong disability. This research identified genetic factors in 8% of cases, with additional likely pathogenic variants in 13% of cases and other potential insights from mouse models in 9% (30% of cases combined) illustrating the potential utility of OGM for helping to better understand the genetic basis of NTDs.

“While folic acid supplementation has helped to significantly reduce occurrences of NTDs, many parents still grapple with the heartbreak of an NTD without knowing why it happened,” commented Dr. Steve Skinner, president and CEO of GGC. “This study underscores our commitment to helping these families with cutting-edge research, including with novel techniques like OGM and it marks an important step forward, offering them not just scientific progress, but a renewed sense of hope for a better understanding of their child’s condition.”

“This research brings something invaluable – insights into potential genetic drivers for NTDs that may have remained unknown without OGM,” said Erik Holmlin, president and CEO of Bionano. “Optical genome mapping has not only revealed previously undetected genetic variants but has also uncovered rare structural variants that can deepen our understanding of NTDs. I believe the reported findings mark a significant advancement in the field and may improve future patient management and guide future therapeutic interventions.”

The full research publication is available at: https://pubmed.ncbi.nlm.nih.gov/40107724/

About GGC

Established in 1974, The Greenwood Genetic Center (GGC) is a non-profit organization committed to advancing medical genetics and providing compassionate care for families affected by genetic diseases and birth defects. Situated in Greenwood, South Carolina, GGC’s expert team of physicians and scientists offers comprehensive clinical genetic services, state-of-the-art diagnostic laboratory testing, educational programs, and impactful research initiatives. With a mission to develop preventative and curative therapies, GGC extends its reach across South Carolina, offering essential resources through satellite offices in Charleston, Columbia, Florence, and Greenville. With over five decades of experience, the organization remains steadfast in its dedication to transforming lives and contributing to the field of medical genetics. For more information, visit ggc.org

About Bionano

Bionano is a provider of genome analysis solutions that can enable researchers and clinicians to reveal answers to challenging questions in biology and medicine. The Company’s mission is to transform the way the world sees the genome through optical genome mapping (OGM) solutions, diagnostic services and software. The Company offers OGM solutions for applications across basic, translational and clinical research. The Company also offers an industry-leading, platform-agnostic genome analysis software solution, and nucleic acid extraction and purification solutions using proprietary isotachophoresis (ITP) technology. Through its Lineagen, Inc. d/b/a Bionano Laboratories business, the Company also offers OGM-based diagnostic testing services.

For more information, visit www.bionano.com or www.bionanolaboratories.com.

Bionano’s products are for research use only and not for use in diagnostic procedures.

Forward-Looking Statements of Bionano Genomics

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “believe,” “can,” “may,” “expect,” “would” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements describe future expectations, plans, results, or strategies, among other things, and in this release include, but are not limited to, statements regarding OGM’s ability to detect SVs compared to traditional cytogenetic methods including KT, CMA and NGS; OGM’s ability to detect SVs relevant to NTDs; the utility of OGM in detecting potential genetic bases for NTDs; the ability of OGM to detect previously unknown SVs that may be relevant to NTDs; the potential of SVs detected by OGM to deepen our understanding of NTDs; the potential ability and utility of SVs detected by OGM to improve future patient care or guide future therapeutic interventions; and other statements that are not of historical fact. Such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events, or results to differ materially from those projected in the forward-looking statements. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the impact of adverse geopolitical and macroeconomic events, such as recent and future bank failures, the ongoing conflicts between Ukraine and Russia and in the Middle East and related sanctions and any regional or global pandemics, on our business and the global economy; failure of our ability to drive adoption and utilization of optical genome mapping as a replacement to traditional cytogenetic techniques; challenges inherent in developing, manufacturing and commercializing products; our ability to further deploy new products and applications for our technology platforms; our expectations and beliefs regarding future growth of the business and the markets in which we operate; changes in our strategic and commercial plans; the failure of OGM to detect SVs compared to traditional cytogenetic methods including KT, CMA and NGS; the failure of OGM to detect SVs relevant to NTDs; the failure of SVs detected by OGM to prove useful for understanding NTDs; the failure of OGM to detect previously unknown SVs that may be relevant to NTDs; the failure of OGM to deepen our understanding of NTDs; the failure of SVs detected by OGM to prove useful to improve future patient care or guide future therapeutic interventions; the failure of OGM use to grow in the research applications reported in this press release; future publications that contradict the findings of the publication referenced in this press release; our ability to continue as a “going concern,” which requires us to manage costs and obtain significant additional financing to fund our strategic plans and commercialization efforts; our ability to consummate any strategic alternatives; the risk that if we fail to obtain additional financing we may seek relief under applicable insolvency laws; and other risks and uncertainties including those described in our filings with the Securities and Exchange Commission (“SEC”), including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2023 and in other filings subsequently made by us with the SEC. All forward-looking statements contained in this report speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. We are under no duty to update any of these forward-looking statements after the date they are made to conform these statements to actual results or revised expectations, except as required by law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date the statements are made. Moreover, except as required by law, neither we nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements contained in this press release.

CONTACTS
Company Contact:
Erik Holmlin, CEO
Bionano Genomics, Inc.
+1 (858) 888-7610
eholmlin@bionano.com

Investor Relations:
David Holmes
Gilmartin Group
+1 (858) 888-7625
IR@bionano.com

FAQ

What are the key findings of BNGO's neural tube defects study using optical genome mapping?

The study found pathogenic structural variants in 8% of cases, variants affecting known NTD pathway genes in 13%, and variants linked to NTD-associated genes from mouse models in 9%, totaling insights in 30% of cases.

Which new candidate genes for neural tube defects did BNGO's research identify?

The research identified four novel candidate genes: RMND5A, HNRNPC, FOXD4, and RBBP4, and expanded clinical implications for AMER1 and TGIF1.

How does BNGO's optical genome mapping compare to traditional methods in detecting NTD variants?

OGM detected pathogenic variants in 8% of cases, compared to approximately 6% detection rate for traditional methods like karyotyping and chromosomal microarray.

What is the global impact of neural tube defects according to BNGO's research?

Neural tube defects impact approximately 300,000 births annually worldwide and remain a leading cause of infant mortality and lifelong disability.