Clinical and functional consequences of GRIA variants in patients with neurological diseases

XiangWei, Wenshu; Perszyk, Riley E.; Liu, Nana; Xu, Yuchen; Bhattacharya, Subhrajit; Shaulsky, Gil H.; Smith-Hicks, Constance; Fatemi, Ali; Fry, Andrew E.; Chandler, Kate; Wang, Tao; Vogt, Julie; Cohen, Julie S.; Paciorkowski, Alex R.; Poduri, Annapurna; Zhang, Yuehua; Wang, Shuang; Wang, Yuping; Zhai, Qiongxiang; Fang, Fang; Leng, Jie; Garber, Kathryn; Myers, Scott J.; Jauss, Robin-Tobias; Park, Kristen L.; Benke, Timothy A.; Lemke, Johannes R.; Yuan, Hongjie; Jiang, Yuwu; Traynelis, Stephen F.

doi:10.1007/s00018-023-04991-6

Cited by 2 publications

(1 citation statement)

References 46 publications

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“…At present, researchers found that GRIA1 encodes AMPA receptors mediated a fast component of the synaptic current. The variants of GRIA1will contribute to neurological conditions disorder [ 48 ]. PCSK9 is a member of the pro-protein convertase family, and plays important roles in proteolytic activation, modification, and degradation of secreted proteins [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of eight lysosomes-related genes signatures and correlation with immune cell infiltration in lung adenocarcinoma

Song,

Zhao,

Zhao

et al. 2023

Cancer Cell Int

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Lung cancer is the leading cause of cancer-related death. Lysosomes are key degradative compartments that maintain protein homeostasis. In current study, we aimed to construct a lysosomes-related genes signature to predict the overall survival (OS) of patients with Lung Adenocarcinoma (LUAD). Differentially expressed lysosomes-related genes (DELYs) were analyzed using The Cancer Genome Atlas (TCGA-LUAD cohort) database. The prognostic risk signature was identified by Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox proportional hazards regression and multivariate Cox analysis. The predictive performance of the signature was assessed by Kaplan–Meier curves and Time-dependent receiver operating characteristic (ROC) curves. Gene set variant analysis (GSVA) was performed to explore the potential molecular biological function and signaling pathways. ESTIMATE and single sample gene set enrichment analysis (ssGSEA) were applied to estimate the difference of tumor microenvironment (TME) between the different risk subtypes. An eight prognostic genes (ACAP3, ATP8B3, BTK, CAV2, CDK5R1, GRIA1, PCSK9, and PLA2G3) signature was identified and divided patients into high-risk and low-risk groups. The prognostic signature was an independent prognostic factor for OS (HR > 1, p < 0.001). The molecular function analysis suggested that the signature was significantly correlated with cancer-associated pathways, including angiogenesis, epithelial mesenchymal transition, mTOR signaling, myc-targets. The low-risk patients had higher immune cell infiltration levels than high-risk group. We also evaluated the response to chemotherapeutic, targeted therapy and immunotherapy in high- and low-risk patients with LUAD. Furthermore, we validated the expression of the eight gene expression in LUAD tissues and cell lines by qRT-PCR. LYSscore signature provide a new modality for the accurate diagnosis and targeted treatment of LUAD and will help expand researchers’ understanding of new prognostic models.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of eight lysosomes-related genes signatures and correlation with immune cell infiltration in lung adenocarcinoma

Song,

Zhao,

Zhao

et al. 2023

Cancer Cell Int

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Unraveling GRIA1 neurodevelopmental disorders: Lessons learned from the p.(Ala636Thr) variant

Tvergaard,

Tkemaladze,

Stödberg

et al. 2024

Clinical Genetics

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Ionotropic glutamate receptors (iGluRs), specifically α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors (AMPARs), play a crucial role in orchestrating excitatory neurotransmission in the brain. AMPARs are intricate assemblies of subunits encoded by four paralogous genes: GRIA1‐4. Functional studies have established that rare GRIA variants can alter AMPAR currents leading to a loss‐ or gain‐of‐function. Patients affected by rare heterozygous GRIA variants tend to have family specific variants and only few recurrent variants have been reported. We deep‐phenotyped a cohort comprising eight unrelated children and adults, harboring a recurrent and well‐established disease‐causing GRIA1 variant (NM_001114183.1: c.1906G>A, p.(Ala636Thr)). Recurrent symptoms included motor and/or language delay, mild–severe intellectual disability, behavioral and psychiatric comorbidities, hypotonia and epilepsy. We also report challenges in social skills, autonomy, living and work situation, and occupational levels. Furthermore, we compared their clinical manifestations in relation to those documented in patients presenting with rare heterozygous variants at analogous positions within paralogous genes. This study provides unprecedented details on the neurodevelopmental outcomes, cognitive abilities, seizure profiles, and behavioral abnormalities associated with p.(Ala636Thr) refining and broadening the clinical phenotype.

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Clinical and functional consequences of GRIA variants in patients with neurological diseases

Cited by 2 publications

References 46 publications

Identification and validation of eight lysosomes-related genes signatures and correlation with immune cell infiltration in lung adenocarcinoma

Identification and validation of eight lysosomes-related genes signatures and correlation with immune cell infiltration in lung adenocarcinoma

Unraveling GRIA1 neurodevelopmental disorders: Lessons learned from the p.(Ala636Thr) variant

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