Yuan Meng, Zhang Jia, Li Yang, Luo Huan, Zhang Jinxiu, Gan Jing
Abstract
ObjectiveTo investigate the clinical phenotype and genetic basis of a child with epilepsy and global developmental delay.
MethodsA 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.
ResultsThe 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.
ConclusionThe 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.
Key words:
Epilepsy; Global developmental delay; Macrocephaly; PAK1 gene; Whole exome sequencing; Child
Contributor Information
Yuan Meng
Department of Pediatrics, Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Chengdu, Sichuan 610041, China
Zhang Jia
Department of Pediatrics, Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Chengdu, Sichuan 610041, China
Li Yang
Department of Pediatrics, Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Chengdu, Sichuan 610041, China
Luo Huan
Department of Pediatrics, Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Chengdu, Sichuan 610041, China
Zhang Jinxiu
Department of Pediatrics, Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Chengdu, Sichuan 610041, China
Gan Jing
Department of Pediatrics, Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Chengdu, Sichuan 610041, China
