Pandey Himani, Sharma Jyoti, Kumar Sourabh, Mohan Nakul, Jain Vishesh, Dhua Anjan Kumar, Yadav Devendra Kumar, Dubey Ashish Kumar, Choudhury Prativa, Goel Prabudh
Laboratory Head, Redcliffe Laboratories, Noida, Uttar Pradesh, India.
Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, India.
J Indian Assoc Pediatr Surg. 2025 May-Jun;30(3):290-295. doi: 10.4103/jiaps.jiaps_217_24. Epub 2025 Apr 28.
The etiology of spina bifida is multifactorial; the phenotype is the end result of both genetic and environmental influences. While whole exome sequencing has identified several pathogenic variants in Indian cohorts, the role of chromosomal imbalances and long contiguous stretches of homozygosity (LCSHs) remains largely unexplored in this population. Chromosomal microarray analysis (CMA) is an important tool that provides insights into such genetic aberrations, making it significant for evaluating patients with spina bifida.
To identify LCSHs and chromosomal imbalances in three spina bifida patients through CMA analysis as a pilot investigation.
Genomic DNA was isolated from three spina bifida patients (P1: 10-year-old female, P2: 1-year-old male, and P3: 2.8-year-old male) and subjected to CMA using the Affymetrix 750K high-density array platform. The submicroscopic chromosomal imbalances and LCSHs were cross-referenced with public databases (Database of Genomic Variants, ClinVar, and OMIM) to evaluate their clinical significance. Functional annotations of the affected genes were performed to understand their role in neural tube development.
CMA revealed significant LCSH on chromosomes 2, 3, and 7 involving the genes , , , , and , all of which are involved in neural tube closure. Mosaic Klinefelter syndrome (25.9% mosaicism) was identified in the second patient while the third patient had a normal genetic profile. The detection of significant genetic variations in two of three cases underscores the potential utility of CMA in spina bifida patients.
This study has generated valuable insights into the complex genetic landscape underlying the multifactorial etiopathogenesis of spina bifida. The findings not only underscore the importance of an integrated approach but also support the cause of a platform for large-scale investigations in the Indian population.
脊柱裂的病因是多因素的；其表型是遗传和环境影响的最终结果。虽然全外显子测序已在印度人群中鉴定出几种致病变异，但染色体失衡和长片段纯合性（LCSHs）在该人群中的作用仍 largely 未被探索。染色体微阵列分析（CMA）是一种重要工具，可深入了解此类基因畸变，对评估脊柱裂患者具有重要意义。
通过 CMA 分析作为一项试点研究，在三名脊柱裂患者中鉴定 LCSHs 和染色体失衡。
从三名脊柱裂患者（P1：10 岁女性，P2：1 岁男性，P3：2.8 岁男性）中分离基因组 DNA，并使用 Affymetrix 750K 高密度阵列平台进行 CMA。将亚微观染色体失衡和 LCSHs 与公共数据库（基因组变异数据库、ClinVar 和 OMIM）进行交叉参考，以评估其临床意义。对受影响基因进行功能注释，以了解它们在神经管发育中的作用。
CMA 显示在染色体 2、3 和 7 上存在显著的 LCSH，涉及基因 、 、 、 和 ，所有这些基因都参与神经管闭合。在第二名患者中鉴定出嵌合型克兰费尔特综合征（25.9%嵌合率），而第三名患者具有正常的基因图谱。在三例中的两例中检测到显著的基因变异，凸显了 CMA 在脊柱裂患者中的潜在效用。
本研究对脊柱裂多因素病因发病机制背后复杂的遗传格局产生了有价值的见解。这些发现不仅强调了综合方法的重要性，还支持了在印度人群中进行大规模研究的平台的事业。
