ALDH7A1 gene
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Clinical Features and Genetic Variants in Chinese Children With Pyridoxine-Dependent Epilepsy
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Six pediatric patients diagnosed with PDE at Linyi People's Hospital between January 2017 and December 2023 were selected as the study subjects... A clinical registry was established, encompassing details such as name, gender, age of onset, predisposing factors, seizure type, seizure frequency and duration, medication history, perinatal condition, neurodevelopment, family history of epilepsy, video electroencephalogram (VEEG), cranial magnetic resonance imaging (MRI), and blood and urine metabolic screening. The children's progress was monitored via routine outpatient visits and phone calls to track adjustments to their medication, epilepsy control, VEEG changes, and neurodevelopmental outcomes later in life. The study received review and approval from the Ethics Committee of Linyi People's Hospital (13003), and all guardians of the children provided informed consent by signing a form. 2.2 | Genetic testing and pathogenicity analyses Anticoagulation tubes with Ethylene Diamine Tetraacetic Acid (EDTA) were used to collect 2 ml of peripheral blood samples from each affected child and their primary family members. Genomic DNA was extracted using the QIAamp Whole Blood DNA Kit (Qiagen, Germany), and whole exome sequencing was conducted. The sequencing data were compared to the human reference genome (hg38 version) using BWA software. Single nucleotide variants and insertion/deletion variants were analyzed using GATK software. The frequencies of variant sites in the Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD), and 1000 Genomes Project (1000G) were queried. Protein structure prediction software, including SIFT, Mutation Taster, and GERP++, was used to predict the deleterious properties of variants.Variants were analyzed for multiple homologous direct biological conservatisms. Protein structure prediction of variant expression was performed using Swiss-Model software. Protein structure visualization analysis was conducted using PyMOL software. The pathogenicity of the variants was assessed in accordance with the American College of Medical Genetics (ACMG) guidelines [11]. Sanger sequencing was carried out to validate the suspected pathogenic variant sites.