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IQSEC2

Gene product: IQ Motif And Sec7 Domain ArfGEF2.

Protein function: It is a component of the postsynaptic density of excitatory synapses and can regulate the responses mediated by glutamate receptors at excitatory synapses. It is also involved in transmembrane transport, lipid transformation and actin cytoskeleton reorganization, and plays an important role in learning processes and memory mechanisms [4].

Phenotype: X-linked mental retardation (XLD)[1]; Infantile Epileptic Spasms Syndrome (XLD)[2]; Lennox-Gastaut Syndrome (XLD)[3].

Mutation database: ClinVar.

Clinical research: PubMed（PMID: 38851096 (Seizure. 2024)；30206421 (Genet Med. 2019)）

Medication reminder: The medication is mainly selected according to the epilepsy syndrome, which is often refractory to anti-epileptic drugs. There are reports of good results after the use of perampanel (one case was topiramate plus perampanel, and there were also reports of poor results after the use of perampanel) [2, 4-5]. There are also reports that children with this gene mutation have fewer epileptic seizures after fever. One case reported that after 40°C massage hot bath treatment, epileptic seizures and autistic symptoms were improved, and this was verified in the corresponding mouse experiments with this gene mutation [6-8]. In addition, there are reports of good response to steroid hormones (there are also reports of poor response) [2, 9].

 

References:

  1. Novel Missense Mutation A789V in IQSEC2 Underlies X-Linked Intellectual Disability in the MRX78 Family. Front Mol Neurosci. 2016 Jan 11:8:85.
  2. Genotypes and phenotypes of IQSEC2 gene variants related epilepsy. Zhonghua Er Ke Za Zhi. 2022 Dec 2;60(12):1317-1321.
  3. A Novel X-Linked Variant of IQSEC2 is Associated with Lennox-Gastaut Syndrome and Mild Intellectual Disability in Three Generations of a Korean Family. Genet Test Mol Biomarkers. 2020 Jan;24(1):54-58.
  4. Perampanel treatment in IQSEC2-associated epileptic encephalopathy. Zh Nevrol Psikhiatr Im S S Korsakova. 2025;125(2):143-149.
  5. Electroencephalographic findings and genetic characterization of two brothers with IQSEC2 pathogenic variant. Brain Dev, 2021, 43(5):652‐656.
  6. Reduction in seizure burden in a child with a A350V IQSEC2 mutation using heat therapy with a Jacuzzi. Clin Case Rep. 2021 Aug 30;9(9):e04734.
  7. Housing of A350V IQSEC2 pups at 37 °C ambient temperature prevents seizures and permits the development of social vocalizations in adulthood. Int J Hyperthermia. 2021;38(1):1495-1501.
  8. Daily Brief Heat Therapy Reduces Seizures in A350V IQSEC2 Mice and Is Associated with Correction of AMPA Receptor-Mediated Synaptic Dysfunction. Int J Mol Sci. 2023 Feb 15;24(4):3924.
  9. Response to Steroids in IQSEC2-Related Encephalopathy Presenting with Rett-Like Phenotype and Infantile Spasms. J Pediatr Genet. 2020 Dec 7;12(1):76-80.