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DOI: 10.1055/s-0041-1739133
SLC7A3: In Silico Prediction of a Potential New Cause of Childhood Epilepsy
Abstract
We report an in-depth genetic analysis in an 11-year-old boy with drug-resistant, generalized seizures and developmental disability. Three distinct variants of unknown clinical significance (VUS) were detected by whole exome sequencing (WES) but not by initial genetic analyses (microarray and epilepsy gene panel). These variants involve the SLC7A3, CACNA1H, and IGLON5 genes, which were subsequently evaluated by computational analyses using the InterVar tool and MutationTaster. While future functional studies are necessary to prove the pathogenicity of a certain VUS, segregation analyses over three generations and in silico predictions suggest the X-linked gene SLC7A3 (transmembrane solute carrier transporter) as the likely culprit gene in this patient. In addition, a search via GeneMatcher unveiled two additional patients with a VUS in SLC7A3. We propose SLC7A3 as a likely candidate gene for epilepsy and/or developmental/cognitive delay and provide an overview of the 27 SLC genes related to epilepsy by other preclinical and/or clinical studies.
Author Contributions
All authors have made substantial contributions to conception and design, data acquisition, analysis and interpretation, and drafting the article. J.S.: conceptualization, methodology, formal analysis, investigation, resources, data curation, writing, visualization; K.J.: conceptualization, writing, supervision; D.M. and R.G.: formal analysis, conceptualization, investigation, resources, writing.
T.B.H., R.S.M., N.G., and L.O.: formal analysis, resources, data curation, writing; L.L.: conceptualization, investigation, writing, supervision.
Ethical Statements and Informed Consent
We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Highest ethical standard was maintained during the study. Parents' informed consent was taken. All procedures performed in our study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Publication History
Received: 04 March 2021
Accepted: 17 September 2021
Article published online:
06 December 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
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