GRM7 deficiency, from excitotoxicity and neuroinflammation to neurodegeneration: Systematic review of GRM7 deficient patients
Bibliographic record
Abstract
The metabotropic glutamate receptor 7 (mGluR7) is a presynaptic G-protein-coupled glutamate receptor that modulates neurotransmitter release and synaptic plasticity at presynaptic terminals. It is encoded by GRM7, and recently variants have been identified in patients with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), developmental delay (DD), intellectual disability (ID), and brain malformations. To gain updated insights into the function of GRM7 and the phenotypic spectrum of genetic variations within this gene, we conducted a systematic review of relevant literature utilizing PubMed, Web of Science, and Scopus databases. Among the 14 articles meeting the inclusion criteria, a total of 42 patients (from 28 families) harboring confirmed mutations in the GRM7 gene have been documented. Specifically, there were 17 patients with heterozygous mutations, 20 patients with homozygous mutations, and 5 patients with compound heterozygous mutations. Common clinical features included intellectual behavioral disability, seizure/epilepsy, microcephaly, developmental delay, peripheral hypertonia and hypomyelination. Genotype-phenotype correlation was not clear and each variant had unique characteristics including gene dosage, mutant protein surface expression, and degradation pathway that result with a spectrum of phenotype manifestations through ASD or ADHD to severe DD/ID with brain malformations. Neuroinflammation may play a role in the development and/or progression of GRM7-related neurodegeneration along with excitotoxicity. The clinical and functional data presented here demonstrate that both autosomal dominant and recessive inheritance of GRM7 mutation can cause disease spectrum phenotypes through ASD or ADHD to severe DD/ID and seizure with brain malformations.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.013 | 0.012 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".