Hemorrhagic shock and encephalopathy syndrome (HSES) is a serious condition that requires intensive care and is associated with a high mortality rate. However, its pathogenesis remains unclear. In the present study, a genetic analysis was performed to determine the genetic background of patients with clinically suspected Dravet syndrome (DS) who developed HSES.
Whole exome sequencing was performed, followed by minigene analysis of the intron variant detected by whole exome sequencing to confirm its effect on splicing.
Whole exome sequencing revealed a novel 21-bp deletion in intron 3 of SCN1A NM_001165963.4 (NC_000002.11:g.166073675_166073695del). This deletion was not found in the patient’s parents and was proven to be de novo. Minigene analysis revealed an aberrant mRNA lacking 40 and 106 bp from the 5′ end of exon 4 of SCN1A. Therefore, we diagnosed this case as DS due to the deletion in intron 3 of SCN1A.
We report a case of DS with HSES caused by a 21-bp deletion in the intron of SCN1A that was confirmed by minigene analysis. The present case met Levin's criteria for HSES and the splicing analysis of SCN1A is an important finding. This study has important implications for understanding HSES pathogenesis.
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Published online: February 09, 2023
Accepted: January 30, 2023
Received in revised form: January 29, 2023
Received: November 16, 2022
Publication stageIn Press Corrected Proof
© 2023 Published by Elsevier B.V. on behalf of The Japanese Society of Child Neurology. All rights reserved.