Clinical and molecular diagnostic study of 320 Chinese children with epilepsy by Genome Sequencing

Abstract

Purpose: To evaluate the diagnostic value of Genome Sequencing(GS) in children with epilepsy. Methods: We performed GS on 320 Chinese children with epilepsy and interpreted Single Nucleotide Variants (SNVs) and Copy Number Variant (CNVs) of all samples. The complete pedigree and clinical data of the probands were established and followed up. The clinical phenotypes, treatments, prognoses and genotypes of the patients were analyzed. Results: Pathogenic/likely pathogenic variants were found in 122 of 320 children (38.13%), of whom, 92 (28.8%) had SNVs, 27 (8.4%) had CNVs, and three had both SNVs and CNVs. Among these variants, there were 3 CNVs of <100K in length. The most frequently mutated gene was SCN1A (10.9%,10/92), which is related to Dravet Syndrome, followed by PRRT2 (8.7%,8/92), which is relevant to benign familial infantile epilepsy, TSC2 (7.6%,7/92), which is associated with Tuberous Sclerosis. The most common recurrent CNVs were 17p13.3 deletion (18.5%, 5/27), 16p11.2 deletion syndrome (14.8%, 4/27), 15q11.2 deletion (11.1%, 3/27), which are related to epilepsy, developmental retardation and congenital abnormalities. The diagnostic yield was higher as the age of seizure onset was smaller. The highest detection rate was 75% in whom developed seizures within one month after birth. 13.4% (43/320) cases were identified to be treatable based on GS. 1% (3/320) of epilepsy patients received direct therapeutic measures and demonstrated favorable prognosis. Conclusion: GS can complete the genetic diagnosis, individualized treatment, and family reproductive guidance for patients. GS can replace Exome Sequencing and Chromosomal Microarray Analysis and is expected to be the first choice of genetic testing method for patients with epilepsy. Key Words: epilepsy; Genome Sequencing; Copy Number Variant; seizure; Single Nucleotide Variations

Genome sequencing using machine learning with a special focus on tuberculosis

“…Researchers then used the algorithm to spot mutations in different tissues-2,658 samples from the Pan-Cancer Whole Genome Analysis dataset [8].A genome sequencing is performed 320 Chinese children with epilepsy were studied, and single-nucleotide and copy number variations were evaluated in all samples. The probands' entire lineage and clinical data were established and followed up on [9].…”

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