Related Experiment Video

Updated: Jan 14, 2026

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
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Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Published on: June 6, 2025

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Novel PAK1 variants related to a variable phenotypic spectrum ranging from mild developmental delay to infantile

Ting Wang1, Shijia Ouyang1, Dongfang Zou2

  • 1Children's Medical Center of Peking University First Hospital, Beijing 102627, China.

Seizure
|October 22, 2025
PubMed
Abstract

Insights

This study identified five new de novo PAK1 variants in patients with PAK1-related disorders, revealing a broad spectrum of phenotypes including epilepsy and macrocephaly. The Leu470Pro variant was the first reported mosaic variant in PAK1.

Area of Science:

  • Genetics
  • Molecular Biology
  • Neurology

Background:

  • PAK1-related disorder is a genetic condition associated with various neurological and developmental abnormalities.
  • Understanding novel variants and their phenotypic spectrum is crucial for diagnosis and management.

Purpose of the Study:

  • To identify novel variants in the PAK1 gene.
  • To explore the phenotypic spectrum of patients with PAK1-related disorders.

Main Methods:

  • Whole-exome sequencing was used to identify variants in five patients.
  • Protein modeling was employed to analyze the damaging effects of identified variants.

Main Results:

  • Five de novo missense PAK1 variants were identified, including the first reported mosaic variant (Leu470Pro).
  • Patients exhibited a range of phenotypes, including epilepsy (81.25%), macrocephaly, and developmental delay/intellectual disability.
  • Infantile epileptic spasms syndrome (IESS) was identified as a rare phenotype associated with PAK1-related epilepsy.

Conclusions:

  • All identified variants in PAK1-related disorders are missense.
  • PAK1-related disorders present a wide phenotypic spectrum, with epilepsy and macrocephaly being common features.
  • Febrile seizures are prevalent in over half of patients with epilepsy.
Keywords:
Developmental delayInfantile epileptic spasms syndromePAK1Phenotypic spectrum

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