探索与GRIN相关的神经发育障碍中的基因-表型关系。
Exploring gene-phenotype relationships in GRIN-related neurodevelopmental disorders.
作者信息
Cha Jong Ho, Kim Jee Min, Yun Hee-Jeong, Chin Hyungjin, Kim Hye Jin, Kim Woojoong, Kim Soo Yeon, Lim Byung Chan, Kim Ki Joong, Lee Seungbok, Chae Jong-Hee
机构信息
Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, South Korea.
Department of Genomic Medicine, Seoul National University Hospital, Seoul, South Korea.
出版信息
NPJ Genom Med. 2025 May 15;10(1):40. doi: 10.1038/s41525-025-00499-z.
The GRIN family is implicated in neurological disorders, such as global developmental delay (GDD) and epilepsy. We reviewed 31 patients with GRIN-related neurodevelopmental disorders at Seoul National University Hospital; all exhibited profound GDD, with 58.1% unable to walk independently and 74.2% unable to speak meaningful words. In a pooled analysis with the GRIN portal data ( https://grin-portal.broadinstitute.org/ ), patients with missense or in-frame variants had significantly higher rates of profound GDD (74.3% vs. 30.4%, p < 0.001) and movement disorders (69.0% vs. 41.4%, p < 0.01) than those with protein-truncating variants. Furthermore, missense or in-frame variants in the M3 and M4 helices of the transmembrane domain were significantly associated with profound GDD (M3 helix: adjusted odds ratio [aOR] 8.48; 95% confidence interval [CI] 2.79-25.76; M4 helix: aOR 3.14; 95% CI 1.39-7.09) compared to those in other domains. Our findings highlight the importance of detailed variant characterization to inform personalized treatment strategies.
GRIN家族与神经疾病有关，如全面发育迟缓（GDD）和癫痫。我们回顾了首尔国立大学医院31例与GRIN相关的神经发育障碍患者；所有患者均表现出严重的全面发育迟缓，58.1%的患者无法独立行走，74.2%的患者无法说出有意义的词语。在与GRIN门户数据（https://grin-portal.broadinstitute.org/）的汇总分析中，错义或框内变异患者的严重全面发育迟缓（74.3%对30.4%，p<0.001）和运动障碍（69.0%对41.4%，p<0.01）发生率显著高于蛋白质截短变异患者。此外，与其他结构域相比，跨膜结构域M3和M4螺旋中的错义或框内变异与严重全面发育迟缓显著相关（M3螺旋：调整优势比[aOR]8.48；95%置信区间[CI]2.79-25.76；M4螺旋：aOR 3.14；95%CI 1.39-7.09）。我们的研究结果强调了详细变异特征分析对制定个性化治疗策略的重要性。
Zotero 插件