Exploring gene-phenotype relationships in GRIN-related neurodevelopmental disorders
Abstract 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 a...
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| Format: | Article |
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Nature Portfolio
2025-05-01
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| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-025-00499-z |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jong Ho Cha |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-b6e3e3d294934b62b10cd18dcf9d866f |
| institution | OA Journals |
| issn | 2056-7944 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj-art-b6e3e3d294934b62b10cd18dcf9d866f2025-08-20T02:25:17ZengNature Portfolionpj Genomic Medicine2056-79442025-05-0110111010.1038/s41525-025-00499-zExploring gene-phenotype relationships in GRIN-related neurodevelopmental disordersJong Ho Cha0Jee Min Kim1Hee-Jeong Yun2Hyungjin Chin3Hye Jin Kim4Woojoong Kim5Soo Yeon Kim6Byung Chan Lim7Ki Joong Kim8Seungbok Lee9Jong-Hee Chae10Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalDepartment of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalDepartment of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalDepartment of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalDepartment of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalDepartment of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalDepartment of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalDepartment of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalDepartment of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalDepartment of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalDepartment of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalAbstract 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.https://doi.org/10.1038/s41525-025-00499-z |
| spellingShingle | 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 Exploring gene-phenotype relationships in GRIN-related neurodevelopmental disorders npj Genomic Medicine |
| title | Exploring gene-phenotype relationships in GRIN-related neurodevelopmental disorders |
| title_full | Exploring gene-phenotype relationships in GRIN-related neurodevelopmental disorders |
| title_fullStr | Exploring gene-phenotype relationships in GRIN-related neurodevelopmental disorders |
| title_full_unstemmed | Exploring gene-phenotype relationships in GRIN-related neurodevelopmental disorders |
| title_short | Exploring gene-phenotype relationships in GRIN-related neurodevelopmental disorders |
| title_sort | exploring gene phenotype relationships in grin related neurodevelopmental disorders |
| url | https://doi.org/10.1038/s41525-025-00499-z |
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