Abstract
Objective
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.
Methods
Whole exome sequencing was performed, followed by minigene analysis of the intron
variant detected by whole exome sequencing to confirm its effect on splicing.
Results
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.
Conclusions
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.
Keywords
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References
- Elevated cytokine, chemokine, and growth and differentiation factor-15 levels in hemorrhagic shock and encephalopathy syndrome: A retrospective observational study.Cytokine. 2021; 137155324
- Growth and differentiation factor-15 as a potential prognostic biomarker for status-epilepticus-associated-with-fever: A pilot study.Brain Dev. 2022; 44: 210-220
- Acute encephalopathy associated with influenza and other viral infections.Acta Neurol Scand. 2007; 115: 45-56
- Detailed characteristics of acute encephalopathy with biphasic seizures and late reduced diffusion: 18-year data of a single-center consecutive cohort.J Neurol Sci. 2020; 411116684
- Epidemiological changes of acute encephalopathy in Japan based on national surveillance for 2014–2017.Brain Dev. 2020; 42: 508-514
- Characteristic neuroradiologic features in hemorrhagic shock and encephalopathy syndrome.J Child Neurol. 2015; 30: 468-475
- Haemorrhagic shock and encephalopathy: a new syndrome with a high mortality in young children.Lancet. 1983; 2: 64-67
- Serum biomarker kinetics with three different courses of HHV-6B encephalitis.Brain Dev. 2013; 35: 590-595
- Hemorrhagic shock and encephalopathy syndrome–the markers for an early HSES diagnosis.BMC Pediatr. 2008; 8: 43
- Recurrent acute necrotizing encephalopathy in a boy with RANBP2 mutation and thermolabile CPT2 variant: the first case of ANE1 in Japan.Brain Dev. 2021; 43: 873-878
- A novel hypomorphic CSF1R gene mutation in the Biallelic State leading to fatal childhood neurodegeneration.Neuropediatrics. 2020; 51: 302-306
- An episode of acute encephalopathy with biphasic seizures and late reduced diffusion followed by hemiplegia and intractable epilepsy observed in a patient with a novel frameshift mutation in HNRNPU.Brain Dev. 2018; 40: 813-818
- Variable clinical phenotype in two siblings with Aicardi-Goutières syndrome type 6 and a novel mutation in the ADAR gene.Eur J Paediatr Neurol. 2018; 22: 186-189
- Biallelic mutations in ATP5F1D, which encodes a subunit of ATP synthase, cause a metabolic disorder.Am J Hum Genet. 2018; 102: 494-504
- De novo variants in RHOBTB2, an atypical Rho GTPase gene, cause epileptic encephalopathy.Hum Mutat. 2018; 39: 1070-1075
- Hemorrhagic shock and encephalopathy syndrome in a patient with a de novo heterozygous variant in KIF1A.Brain Dev. 2022; 44: 249-253
- Pathogenic evaluation of synonymous COL4A5 variants in X-linked Alport syndrome using a minigene assay.Mol Genet Genomic Med. 2020; 8: e1342
- Detection of a splice site variant in a patient with glomerulopathy and fibronectin deposits.Nephron. 2018; 138: 166-171
- Cryptic splice activation but not exon skipping is observed in minigene assays of dystrophin c.9361+1G>A mutation identified by NGS.J Hum Genet. 2017; 62: 531-537
- The clinical outcome and neuroimaging of acute encephalopathy after status epilepticus in Dravet syndrome.Dev Med Child Neurol. 2018; 60: 566-573
- Acute encephalopathy in children with Dravet syndrome.Epilepsia. 2012; 53: 79-86
- Mutations of the SCN1A gene in acute encephalopathy.Epilepsia. 2012; 53: 558-564
- Early clinical features and diagnosis of Dravet syndrome in 138 Chinese patients with SCN1A mutations.Brain Dev. 2014; 36: 676-681
- Utility of the Kyoto Scale of Psychological Development in cognitive assessment of children with pervasive developmental disorders.Psychiatry Clin Neurosci. 2009; 63: 241-243
- In vivo and in vitro splicing assay of SLC12A1 in an antenatal salt-losing tubulopathy patient with an intronic mutation.Hum Genet. 2009; 126: 533-538
- Retrospective multiinstitutional study of the prevalence of early death in Dravet syndrome.Epilepsia. 2011; 52: 1144-1149
- Mortality in Dravet syndrome: search for risk factors in Japanese patients.Epilepsia. 2011; 52: 50-54
- GDF15 is an inflammation-induced central mediator of tissue tolerance.Cell. 2019; 178: 1231-1244.e11
- Monoallelic KIF1A-related disorders: a multicenter cross sectional study and systematic literature review.J Neurol. 2022; 269: 437-450
- PEHO syndrome: KIF1A mutation and decreased activity of mitochondrial respiratory chain complex.J Clin Neurosci. 2019; 61: 298-301
- Hemorrhagic shock and encephalopathy syndrome in a quadriplegic child: an argument for the triggering role of impaired thermoregulatory response.Spine (Phila Pa 1976). 2010; : E730-E732
- Effect of higher body temperature and acute brain edema on mortality in hemorrhagic shock and encephalopathy syndrome.J Neurol Sci. 2022; 439120321
- Haemorrhagic shock encephalopathy syndrome in the British Isles.Arch Dis Child. 1992; 67: 985-993
- Haemorrhagic shock encephalopathy syndrome presenting with myoglobinuria.Arch Dis Child. 1996; 74: 168-169
- Pathophysiology of status epilepticus.Neurosci Lett. 2018; 667: 84-91
- Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Genet Med. 2015; 17: 405-424
- Blood RNA analysis can increase clinical diagnostic rate and resolve variants of uncertain significance.Genet Med. 2020; 22: 1005-1014
Article info
Publication history
Published online: February 09, 2023
Accepted:
January 30,
2023
Received in revised form:
January 29,
2023
Received:
November 16,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 Published by Elsevier B.V. on behalf of The Japanese Society of Child Neurology. All rights reserved.
