Goel Prabudh, Sharma Mahima, Kaushik Himani, Kumar Sourabh, Singh Harpreet, Jain Vishesh, Dhua Anjan Kumar, Yadav Devendra Kumar, Kumar Neeta, Agarwala Sandeep
Department of Paediatric Surgery, All India Institute of Medical Sciences, New Delhi, India.
Compute Genomics Pvt. Ltd, New Delhi, India.
J Indian Assoc Pediatr Surg. 2024 Sep-Oct;29(5):529-535. doi: 10.4103/jiaps.jiaps_64_24. Epub 2024 Sep 9.
To identify the genetic markers of spina bifida through a systematic survey of the exome in an Indian cohort.
Three consecutive patients (P1: 1 year, male; P2: 2.8 years, male; and P3: 10 years, female) with spina bifida (lumbosacral meningomyelocele) underwent whole-exome sequencing (libraries: SureSelect Human All Exon V8; sequencing: 2 * 150 bp paired-end run, 100×) with NovaSeq 6000. Data analysis was performed using SMART-One™ (secondary analysis) and SMARTer™ (tertiary analysis) for automated quality check, alignment (GRCh38/hg38), variant calling, annotation (ClinVar, OMIM, avsnp150, 1000 Genomes v5b, ExAC v0.3, gnomAD v4.0, and esp6500vi2all v0.0.25), v0.0.25), interpretation. The pathogenic and likely pathogenic (ClinVar/ InterVar), non-synonymous, exonic markers (read depth ≥ 5) were matched with the Familial Neural Tube Defects (Version 1.10) panel (FNTD panel).
Pathogenic variants overlapping with the FNTD panel were MTRR, CC2D2A, and ZIC2 in P1 and P2, TGIF1 in P1 only, and none in P3. Novel pathogenic/likely pathogenic variants common to all three patients were PRUNE1, PKD1, PDZD2, and DAB2 in the homozygous state as well as in the heterozygous state, PLK1 and NLGN2. The possible role of such markers in etiopathogenesis was explored through a literatur search.
The genetic landscape of the spina bifida in an Indian cohort is diverse compared to that reported from other parts of the world. A comprehensive catalog of single-nucleotide variants in the etiopathogenesis of the spina bifida on a background of the Familial Neural Tube Defects Panel has been generated.
通过对印度队列的外显子组进行系统调查，确定脊柱裂的遗传标记。
三名连续的脊柱裂（腰骶部脊髓脊膜膨出）患者（P1：1岁，男性；P2：2.8岁，男性；P3：10岁，女性）接受了全外显子组测序（文库：SureSelect Human All Exon V8；测序：2×150 bp双端测序，100×），使用NovaSeq 6000进行。数据分析使用SMART-One™（二级分析）和SMARTer™（三级分析）进行自动质量检查、比对（GRCh38/hg38）、变异检测、注释（ClinVar、OMIM、avsnp150、1000 Genomes v5b、ExAC v0.3、gnomAD v4.0和esp6500vi2all v0.0.25）、v0.0.25）、解读。将致病和可能致病（ClinVar/InterVar）、非同义外显子标记（读取深度≥5）与家族性神经管缺陷（版本1.10）面板（FNTD面板）进行匹配。
与FNTD面板重叠的致病变异在P1和P2中为MTRR、CC2D2A和ZIC2，仅在P1中为TGIF1，P3中无。所有三名患者共有的新的致病/可能致病变异在纯合状态以及杂合状态下为PRUNE1、PKD1、PDZD2和DAB2，还有PLK1和NLGN2。通过文献检索探索了这些标记在发病机制中的可能作用。
与世界其他地区报道的情况相比，印度队列中脊柱裂的遗传图谱具有多样性。在家族性神经管缺陷面板的背景下，已生成了脊柱裂发病机制中单核苷酸变异的综合目录。
