Tuncay Islam Oguz, Lee Eun Kyoung, Gustafson Anxhela, Lee Yoonsuh, Jung Dawoon, Koh June-Young, Lee Wonchul, Lee Sangmoon, Shazand Kamran
Inocras Inc., San Diego, CA, USA.
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
NPJ Genom Med. 2025 Oct 10;10(1):67. doi: 10.1038/s41525-025-00520-5.
Adolescent idiopathic scoliosis (AIS) is a complex genetic disorder. This study used whole-genome sequencing (WGS) to investigate the genetic basis of AIS in 119 patients from 103 families. Our WGS analysis identified known pathogenic or protein-truncating variants in 15 probands, and other strong or moderate candidate variants in 69 additional patients. We found both coding and non-coding mutations, including structural variants. Candidate genes included known AIS genes (e.g., COL11A2, FBN1) and genes linked to other musculoskeletal disorders with scoliosis (e.g., RYR1). Association analysis confirmed four known AIS single-nucleotide polymorphisms in our cohort. Gene set enrichment analysis revealed four gene clusters related to skeletal muscle contraction, extracellular matrix, and gene expression regulation. This WGS-based approach identified clinically relevant genetic variations and biological pathways in AIS patients, offering valuable insights into its complex development.
青少年特发性脊柱侧凸（AIS）是一种复杂的遗传性疾病。本研究采用全基因组测序（WGS）对来自103个家庭的119例患者进行AIS遗传基础研究。我们的WGS分析在15名先证者中鉴定出已知的致病或蛋白截短变异，在另外69例患者中鉴定出其他强或中度候选变异。我们发现了编码和非编码突变，包括结构变异。候选基因包括已知的AIS基因（如COL11A2、FBN1）以及与其他伴有脊柱侧凸的肌肉骨骼疾病相关的基因（如RYR1）。关联分析在我们的队列中证实了四个已知的AIS单核苷酸多态性。基因集富集分析揭示了与骨骼肌收缩、细胞外基质和基因表达调控相关的四个基因簇。这种基于WGS的方法在AIS患者中鉴定出临床相关的遗传变异和生物学途径，为其复杂的发病机制提供了有价值的见解。
