Identification of Missense ADGRV1 Mutation as a Candidate Genetic Cause of Familial Febrile Seizure 4

Han, Ji Yoon; Lee, Hyun Joo; Lee, Young Mock; Park, Joonhong

doi:10.3390/children7090144

Cited by 9 publications

(6 citation statements)

References 38 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although several loci for familial FS have been verified, including FEB1 on chromosome 8q13-q21 (MIM number: 121210), FEB2 (602477) on chromosome 19p13, FEB3B (613863) on chromosome 2q24, FEB5 (609255) on chromosome 6q22-q24, FEB6 (609253) on chromosome 18p11, FEB7 (611515) on chromosome 21q22, FEB9 (611634) on chromosome 3p24.2p23, and FEB10 (612637) on chromosome 3q26, disease-associated genes have not been identified on them [ 58 ]. In contrast, genetic mutations were identified in FEB3A (604403), which is affected by SCN1A on chromosome 2q24; FEB4 (604352), which is affected by ADGRV1 on chromosome 5q14; FEB8 (607681), which is affected by GABRG2 on chromosome 5q31; and FEB11 (614418), which is affected by CPA on chromosome 8q13 (56, 58) [ 58 - 60 ].…”

Section: Genetic Factors Identified In Febrile Seizuresmentioning

confidence: 99%

Pathogenetic and etiologic considerations of febrile seizures

Han

2023

Clin Exp Pediatr

Self Cite

View full text Add to dashboard Cite

Febrile seizure (FS), which occurs in febrile children without underlying health problems, is the most common type of seizure disorder in children. The suggested pathogenesis of FS derived from several animal and human studies is multifactorial and debatable. Neuronal hyperexcitability, which de velops during inflammatory responses that accompany fever, provokes seiz ures. However, the exact role of each inflammatory mediator (e.g., cytokines) is undefined in terms of the connection between systemic or local inflammation and the central nervous system, and the mechanisms by which cytokines increase neuronal exci tability remain unclear. In contrast, the cause of fever in most children with FS is usually mild respiratory virus infection (e.g., rhinovirus, influenza virus, adenovirus, and enterovirus) rather than severe bacterial infections. In temperate regions, the major causative respiratory viruses seem to mirror seasonally prevalent respiratory viruses in the community. Therefore, vigo rous efforts to identify the causative pathogen of fever may not be necessary in children with FS. Genetic factors seem to play a role in neuronal hyperexcitability, and some types of genetic variation have been identified in several genes encoding ion channels of neurons that participate in neuronal excitation. Although most children with FS have benign outcomes, some characteristics such as complex FS, febrile status epilepticus, consecutive afebrile seizures, and the presence of neurodevelop mental disabilities may require further genetic and neurologic evaluations.

show abstract

Section: Genetic Factors Identified In Febrile Seizuresmentioning

confidence: 99%

Pathogenetic and etiologic considerations of febrile seizures

Han

2023

Clin Exp Pediatr

Self Cite

View full text Add to dashboard Cite

show abstract

“…Unlike intact animals used in the MES, scPTZ, and 6-Hz models, Frings mice have an underlying pathology accountable for the innate susceptibility to seizures. 38,39 It was thus assumed that soticlestat may modify neurological conditions behind seizure susceptibility. To test the hypothesis, a seizure model with progressive phenotypes was employed.…”

Section: Resultsmentioning

confidence: 99%

Anticonvulsive properties of soticlestat, a novel cholesterol 24‐hydroxylase inhibitor

et al. 2022

View full text Add to dashboard Cite

Objective The formation of 24S‐hydroxycholesterol is a brain‐specific mechanism of cholesterol catabolism catalyzed by cholesterol 24‐hydroxylase (CYP46A1, also known as CH24H). CH24H has been implicated in various biological mechanisms, whereas pharmacological lowering of 24S‐hydroxycholesterol has not been fully studied. Soticlestat is a novel small‐molecule inhibitor of CH24H. Its therapeutic potential was previously identified in a mouse model with an epileptic phenotype. In the present study, the anticonvulsive property of soticlestat was characterized in rodent models of epilepsy that have long been used to identify antiseizure medications. Methods The anticonvulsive property of soticlestat was investigated in maximal electroshock seizures (MES), pentylenetetrazol (PTZ) acute seizures, 6‐Hz psychomotor seizures, audiogenic seizures, amygdala kindling, PTZ kindling, and corneal kindling models. Soticlestat was characterized in a PTZ kindling model under steady‐state pharmacokinetics to relate its anticonvulsive effects to pharmacodynamics. Results Among models of acutely evoked seizures, whereas anticonvulsive effects of soticlestat were identified in Frings mice, a genetic model of audiogenic seizures, it was found ineffective in MES, acute PTZ seizures, and 6‐Hz seizures. The protective effects of soticlestat against audiogenic seizures increased with repetitive dosing. Soticlestat was also tested in models of progressive seizure severity. Soticlestat treatment delayed kindling acquisition, whereas fully kindled animals were not protected. Importantly, soticlestat suppressed the progression of seizure severity in correlation with 24S‐hydroxycholesterol lowering in the brain, suggesting that 24S‐hydroxycholesterol can be aggressively reduced to produce more potent effects on seizure development in kindling acquisition. Significance The data collectively suggest that soticlestat can ameliorate seizure symptoms through a mechanism distinct from conventional antiseizure medications. With its novel mechanism of action, soticlestat could constitute a novel class of antiseizure medications for treatment of intractable epilepsy disorders such as developmental and epileptic encephalopathy.

show abstract

“…A novel heterozygous mutation (c.10601C>T p. Ser3534Leu) in ADGRV 1 was identified in S-5. ADGRV1 mutation has been seen previously associated with familial febrile seizure 4 ( Han et al, 2020 ), which is a febrile disease. Since the patient in our study also presented with recurrent fever without evidence of infection or common autoimmune disease, we propose that the new mutation in ADGRV1 may have an impact on the occurrence of febrile disease in this patient.…”

Section: Discussionmentioning

confidence: 98%

The Application of Whole−Exome Sequencing in Patients With FUO

Guo

Feng

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

BackgroundFever of unknown origin (FUO) is still a challenge for clinicians. Next-generation sequencing technologies, such as whole exome sequencing (WES), can be used to identify genetic defects in patients and assist in diagnosis. In this study, we investigated the application of WES in individuals with FUO.MethodsWe performed whole-exome sequencing on 15 FUO patients. Clinical information was extracted from the hospital information system.ResultsIn 7/15 samples, we found positive results, including potentially causative mutations across eight different genes: CFTR, CD209, IRF2BP2, ADGRV 1, TYK2, MEFV, THBD and GATA2.ConclusionsOur results show that whole-exome sequencing can promote the genetic diagnosis and treatment of patients with FUO.

show abstract

Identification of Missense ADGRV1 Mutation as a Candidate Genetic Cause of Familial Febrile Seizure 4

Cited by 9 publications

References 38 publications

Pathogenetic and etiologic considerations of febrile seizures

Pathogenetic and etiologic considerations of febrile seizures

Anticonvulsive properties of soticlestat, a novel cholesterol 24‐hydroxylase inhibitor

The Application of Whole−Exome Sequencing in Patients With FUO

Contact Info

Product

Resources

About