Department of Orthopedics, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, N1# Shangcheng Road, Yiwu, 322000, Zhejiang Province, China.
Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, China.
J Orthop Surg Res. 2024 Jan 3;19(1):19. doi: 10.1186/s13018-023-04481-2.
Trp3 allele in COL9A3 gene has been widely studied in populations with intervertebral disc disease. We identified a novel pathogenic variant in COL9A3 gene in a pedigree with multiple lumbar disc herniation (LDH). The proband was a 14-year-old boy who developed LDH at the L4/5 and L5/S1 spinal segments. His father, paternal aunt and grandfather were diagnosed with LDH at an age of 35, 30 and 23, respectively. By applying whole exome sequencing, a heterozygous missense variant (c.1150C > T, p.Arg384Trp) in COL9A3 was identified. According to the ACMG guidelines, this variant is predicted to be pathogenic. In addition, prediction tools found COL9A3 protein of this variant a reduced stability, some changed charge properties, and an altered spatial conformation. Findings expanded the mutational spectrum of LDH and contributed to the understanding of COL9A3 in the pathogenesis of LDH.
Trp3 等位基因在 COL9A3 基因中已在椎间盘疾病人群中进行了广泛研究。我们在一个具有多个腰椎间盘突出症 (LDH) 的家族中鉴定出 COL9A3 基因中的一个新的致病变体。先证者是一名 14 岁男孩，他在 L4/5 和 L5/S1 脊柱节段出现 LDH。他的父亲、姑姑和祖父分别在 35、30 和 23 岁时被诊断为 LDH。通过应用全外显子组测序，在 COL9A3 中发现了一个杂合错义变异（c.1150C>T，p.Arg384Trp）。根据 ACMG 指南，该变体被预测为致病性的。此外，预测工具发现该变体的 COL9A3 蛋白稳定性降低，一些电荷特性发生改变，空间构象发生改变。这些发现扩展了 LDH 的突变谱，并有助于理解 COL9A3 在 LDH 发病机制中的作用。
