Brain Behavior & Immunity - Health· 2024Q1· Review
GRM7 deficiency, from excitotoxicity and neuroinflammation to neurodegeneration: Systematic review of GRM7 deficient patients
- 9citations
- Q1SCImago
- 2024year
Short summary
A systematic review of 42 patients with GRM7 gene mutations reveals a spectrum of neurodevelopmental disorders, including intellectual disability, ADHD, and ASD, often accompanied by seizures and brain malformations.
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Key points
- 42 patients from 28 families with GRM7 mutations were identified across 14 studies.
- Common clinical features include intellectual disability, seizures, microcephaly, developmental delay, and hypomyelination.
- Mutations can be heterozygous, homozygous, or compound heterozygous, leading to a spectrum of phenotypes from ASD/ADHD to severe ID with brain malformations.
- Excitotoxicity and neuroinflammation are implicated in the neurodegeneration associated with GRM7 deficiency.
AI-generated from the title and abstract; the full text is not read.
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.
The authors' abstract, as published at the source. Brain Behavior & Immunity - Health, 2024 · DOI ↗
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Field: Genetics (Biochemistry, Genetics and Molecular Biology)
GeneticsBiochemistry, Genetics and Molecular Biology