Optical genome mapping identifies rare structural variants in neural tube defects
Nikhil S Sahajpal1, Jane Dean1, Benjamin Hilton1
1Greenwood Genetic Center, Greenwood, South Carolina 29646, USA.
Genome Research
|March 19, 2025
Summary
Optical genome mapping identified structural variants in neural tube defects (NTDs) cases, revealing new candidate genes and pathways involved in these common birth defects.
Area of Science:
- Genetics
- Developmental Biology
- Medical Genomics
Background:
- Neural tube defects (NTDs) are common central nervous system birth defects with a poorly understood genetic basis.
- Current genetic technologies often miss rare structural variants (SVs) that may contribute to NTDs.
Purpose of the Study:
- To investigate the role of SVs in NTDs using optical genome mapping (OGM).
- To identify novel genes and pathways associated with NTD pathogenesis.
Main Methods:
- Applied OGM to 104 NTD cases (74 isolated, 30 with other malformations).
- Conducted variant analysis using population databases and parental studies.
- Correlated identified SVs with known NTD-associated genes and neural tube development pathways.
Main Results:
- Diagnostic findings were identified in 8% of cases, with candidate findings in an additional 22%.
- SVs impacting genes associated with NTDs in mice were found in 9% of cases.
- SVs affecting neural tube development pathways were identified in 13% of cases.
- Identified RMND5A, HNRNPC, FOXD4, and RBBP4 as strong candidate genes.
- Expanded the phenotypic spectrum of AMER1 and TGIF1 to include NTDs.
Conclusions:
- OGM is effective in detecting SVs contributing to NTDs.
- This study provides key insights into NTD pathogenesis and highlights the role of SVs.
- Identified novel candidate genes and pathways for NTDs, advancing genetic understanding.
