Analysis of clinical features and PAK1 gene variant in a child with epilepsy and global developmental delay / 中华医学遗传学杂志

ABSTRACT

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.