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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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
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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| Summary: | 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. |
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| ISSN: | 2056-7944 |