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.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This research was supported by Science, Technology and Innovation Commission of Shenzhen Municipality under grant No. KJYY20151116165726645.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
the Institutional Review Board On Bioethics and Biosafety of BGI and the ethics committee of the Shenzhen Children's Hospital
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Data Availability
The data that support the findings of this study have been deposited in the CNSA (https://db.cngb.org/cnsa/) of CNGBdb with accession code CNP0000788.