Jong Ho Cha, Jee Min Kim, Hee-Jeong Yun, Hyungjin Chin, Hye Jin Kim, Woojoong Kim, Soo Yeon Kim, Byung Chan Lim, Ki Joong Kim, Seungbok Lee, Jong-Hee Chae
{"title":"探索grin相关神经发育障碍的基因-表型关系。","authors":"Jong Ho Cha, Jee Min Kim, Hee-Jeong Yun, Hyungjin Chin, Hye Jin Kim, Woojoong Kim, Soo Yeon Kim, Byung Chan Lim, Ki Joong Kim, Seungbok Lee, Jong-Hee Chae","doi":"10.1038/s41525-025-00499-z","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"40"},"PeriodicalIF":4.7000,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081769/pdf/","citationCount":"0","resultStr":"{\"title\":\"Exploring gene-phenotype relationships in GRIN-related neurodevelopmental disorders.\",\"authors\":\"Jong Ho Cha, Jee Min Kim, Hee-Jeong Yun, Hyungjin Chin, Hye Jin Kim, Woojoong Kim, Soo Yeon Kim, Byung Chan Lim, Ki Joong Kim, Seungbok Lee, Jong-Hee Chae\",\"doi\":\"10.1038/s41525-025-00499-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":19273,\"journal\":{\"name\":\"NPJ Genomic Medicine\",\"volume\":\"10 1\",\"pages\":\"40\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-05-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081769/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"NPJ Genomic Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41525-025-00499-z\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"NPJ Genomic Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41525-025-00499-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
摘要
GRIN家族与神经系统疾病有关，如全面性发育迟缓（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；所有患儿均表现为重度GDD， 58.1%的患儿不能独立行走，74.2%的患儿不能说有意义的话。在GRIN门户网站数据（https://grin-portal.broadinstitute.org/）的汇总分析中，有错义或帧内变异的患者有显著更高的深度GDD发生率(74.3% vs. 30.4%, p
Exploring gene-phenotype relationships in GRIN-related neurodevelopmental disorders.
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.
NPJ Genomic MedicineBiochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
9.40
自引率
1.90%
发文量
67
审稿时长
17 weeks
期刊介绍：
npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine.
The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
