Genetic Markers of Spina Bifida: Enrichment of Pathogenic Variants and Variants of Uncertain Significance
Introduction: The genetic diversity of the population in India, shaped by its unique history of migrations and varied ethnic landscape, suggests the possibility of genetic profiles distinct from the western populations. Objective: The objective is to investigate the genetic basis of spina bifida in...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2025-03-01
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| Series: | Journal of Indian Association of Pediatric Surgeons |
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| Online Access: | https://journals.lww.com/10.4103/jiaps.jiaps_193_24 |
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| author | Jyoti Sharma Mahima Sharma Sourabh Kumar Himani Kaushik Himani Pandey Devi Lal Vishesh Jain Anjan Kumar Dhua Devendra Kumar Yadav Sandeep Agarwala Prabudh Goel |
| author_facet | Jyoti Sharma Mahima Sharma Sourabh Kumar Himani Kaushik Himani Pandey Devi Lal Vishesh Jain Anjan Kumar Dhua Devendra Kumar Yadav Sandeep Agarwala Prabudh Goel |
| author_sort | Jyoti Sharma |
| collection | DOAJ |
| description | Introduction:
The genetic diversity of the population in India, shaped by its unique history of migrations and varied ethnic landscape, suggests the possibility of genetic profiles distinct from the western populations.
Objective:
The objective is to investigate the genetic basis of spina bifida in the Indian cohort through whole-exome sequencing and pathway enrichment.
Methods:
The variants of uncertain significance (VUS) of spina bifida were identified through whole-exome sequencing in the study cohort (n = 3). The pathogenic, likely pathogenic, and VUS were analyzed for protein–protein interactions and functional associations with genes implicated in spina bifida using tools such as STRING and KEGG pathways, which were validated through a literature review. The study was focused on the Wnt/planar cell polarity signaling pathway, which is crucial for neural tube closure.
Results:
The study-cohort was collectively represented through 40 common VUS, including eight deleterious SNPs related to genes AP3D1, NLRP9, PCDHGA11, PRSS3, MTSS2, ENDOV, C9, and NSD3. These genes were functionally linked to neural development, immune response, and cellular processes critical for neural tube closure. Notably, interactions were observed between four genes (NLGN2, PKD1, PRSS3, and PLK1) and CTNNB1 (Wnt signaling pathway) crucial for embryonic neural tube formation.
Conclusions:
This study has identified novel genetic variants and pathways potentially contributing to the etiopathogenesis of spina bifida in the Indian population. Future research with larger cohorts and functional studies is necessary to validate these findings and explore their potential for clinical applications in spina bifida. |
| format | Article |
| id | doaj-art-6ccc96383b4f455f9437f6796f7d1035 |
| institution | DOAJ |
| issn | 0971-9261 1998-3891 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Journal of Indian Association of Pediatric Surgeons |
| spelling | doaj-art-6ccc96383b4f455f9437f6796f7d10352025-08-20T03:03:37ZengWolters Kluwer Medknow PublicationsJournal of Indian Association of Pediatric Surgeons0971-92611998-38912025-03-0130216316910.4103/jiaps.jiaps_193_24Genetic Markers of Spina Bifida: Enrichment of Pathogenic Variants and Variants of Uncertain SignificanceJyoti SharmaMahima SharmaSourabh KumarHimani KaushikHimani PandeyDevi LalVishesh JainAnjan Kumar DhuaDevendra Kumar YadavSandeep AgarwalaPrabudh GoelIntroduction: The genetic diversity of the population in India, shaped by its unique history of migrations and varied ethnic landscape, suggests the possibility of genetic profiles distinct from the western populations. Objective: The objective is to investigate the genetic basis of spina bifida in the Indian cohort through whole-exome sequencing and pathway enrichment. Methods: The variants of uncertain significance (VUS) of spina bifida were identified through whole-exome sequencing in the study cohort (n = 3). The pathogenic, likely pathogenic, and VUS were analyzed for protein–protein interactions and functional associations with genes implicated in spina bifida using tools such as STRING and KEGG pathways, which were validated through a literature review. The study was focused on the Wnt/planar cell polarity signaling pathway, which is crucial for neural tube closure. Results: The study-cohort was collectively represented through 40 common VUS, including eight deleterious SNPs related to genes AP3D1, NLRP9, PCDHGA11, PRSS3, MTSS2, ENDOV, C9, and NSD3. These genes were functionally linked to neural development, immune response, and cellular processes critical for neural tube closure. Notably, interactions were observed between four genes (NLGN2, PKD1, PRSS3, and PLK1) and CTNNB1 (Wnt signaling pathway) crucial for embryonic neural tube formation. Conclusions: This study has identified novel genetic variants and pathways potentially contributing to the etiopathogenesis of spina bifida in the Indian population. Future research with larger cohorts and functional studies is necessary to validate these findings and explore their potential for clinical applications in spina bifida.https://journals.lww.com/10.4103/jiaps.jiaps_193_24neural tube defectsplanar cell polarityspina bifidavariant of uncertain significancewhole-exome sequencingwnt signaling pathway |
| spellingShingle | Jyoti Sharma Mahima Sharma Sourabh Kumar Himani Kaushik Himani Pandey Devi Lal Vishesh Jain Anjan Kumar Dhua Devendra Kumar Yadav Sandeep Agarwala Prabudh Goel Genetic Markers of Spina Bifida: Enrichment of Pathogenic Variants and Variants of Uncertain Significance Journal of Indian Association of Pediatric Surgeons neural tube defects planar cell polarity spina bifida variant of uncertain significance whole-exome sequencing wnt signaling pathway |
| title | Genetic Markers of Spina Bifida: Enrichment of Pathogenic Variants and Variants of Uncertain Significance |
| title_full | Genetic Markers of Spina Bifida: Enrichment of Pathogenic Variants and Variants of Uncertain Significance |
| title_fullStr | Genetic Markers of Spina Bifida: Enrichment of Pathogenic Variants and Variants of Uncertain Significance |
| title_full_unstemmed | Genetic Markers of Spina Bifida: Enrichment of Pathogenic Variants and Variants of Uncertain Significance |
| title_short | Genetic Markers of Spina Bifida: Enrichment of Pathogenic Variants and Variants of Uncertain Significance |
| title_sort | genetic markers of spina bifida enrichment of pathogenic variants and variants of uncertain significance |
| topic | neural tube defects planar cell polarity spina bifida variant of uncertain significance whole-exome sequencing wnt signaling pathway |
| url | https://journals.lww.com/10.4103/jiaps.jiaps_193_24 |
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