[Analysis of clinical features and PAK1 gene variant in a child with epilepsy and global developmental delay]
Insights
A likely pathogenic variant in the PAK1 gene (c.1427T>C) was identified in a child with epilepsy and global developmental delay. This genetic finding offers crucial insights for diagnosing and counseling similar pediatric cases.
Area of Science:
- Genetics
- Neurology
- Pediatrics
Background:
- Epilepsy and global developmental delay are complex neurological conditions with diverse genetic underpinnings.
- Identifying specific genetic variants is crucial for accurate diagnosis and targeted therapeutic strategies.
Observation:
- A pediatric case presented with epilepsy, global developmental delay, and macrocephaly.
- Whole exome sequencing revealed a de novo likely pathogenic variant (c.1427T>C) in the PAK1 gene.
Findings:
- The identified PAK1 variant (c.1427T>C) was predicted to be deleterious to protein function.
- Bioinformatic analysis and literature review indicated this variant is rare and potentially disease-causing.
- The variant was classified as likely pathogenic according to ACMG guidelines.
Implications:
- This finding expands the known genotype-phenotype correlations for PAK1-related disorders.
- It provides a genetic basis for the observed clinical features in the affected child.
- This case serves as a reference for clinical diagnosis and genetic counseling in pediatric epilepsy and developmental delay.
Objective:
To investigate the clinical phenotype and genetic basis of a child with epilepsy and global developmental delay.
Methods:
A child with epilepsy and global developmental delay who had visited West China Second University Hospital, Sichuan University on April 1, 2021 was selected as the study subject. Clinical data of the child were reviewed. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. A literature review was also carried out by searching databases such as Wanfang data knowledge service platform, China National Knowledge Infrastructure, PubMed, ClinVar and Embase to summarize the clinical phenotypes and genotypes of the affected children.
Results:
The child was a 2-year-and-2-month-old male with epilepsy, global developmental delay and macrocephaly. Results of WES showed that the child has harbored a c.1427T>C variant of the PAK1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Only one similar case had been recorded by the dbSNP, OMIM, HGMD, and ClinVar databases. No frequency for this variant among Asian population was available in the ExAC, 1000 Genomes, and gnomAD databases. Prediction with IFT, PolyPhen-2, LRT, Mutation Taster, and FATHMM online software suggested that this variant is deleterious to the function of encoded protein. Based on the Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics (ACMG), the PAK1 gene c.1427T>C variant was determined to be likely pathogenic.
Conclusion:
The PAK1 gene c.1427T>C variant probably underlay the epilepsy and global developmental delay in this child, which has provided a reference for the clinical diagnosis and genetic counseling in children with similar disorders.
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