Novel Myoclonin1/EFHC1 mutations in Mexican patients with juvenile myoclonic epilepsy

Jara‐Prado, Aurelio; Martínez‐Juárez, Iris E.; Ochoa, Adriana; González, Víctor; Fernández-González-Aragón, María del Carmen; López‐Ruiz, Minerva; Medina, Marco T.; Bailey, Julia N.; Delgado‐Escueta, Antonio V.; Alonso, María Elisa

doi:10.1016/j.seizure.2012.05.016

Cited by 21 publications

(14 citation statements)

References 14 publications

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“…26 We included medical records that had the following variables: VPA dose, blood levels, and length of time taking VPA; if any of these variables were missing, records were excluded. The last taken dose of VPA was recorded, and the patient must have been on that dose for at least one year of monitoring.…”

Section: Methodsmentioning

confidence: 99%

High-dose versus low-dose valproate for the treatment of juvenile myoclonic epilepsy: Going from low to high

Hernández-Vanegas

Jara‐Prado

Ochoa

et al. 2016

Epilepsy & Behavior

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Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy accounting for 3–12% of adult cases of epilepsy. Valproate has proven to be the first-choice drug in JME for controlling the most common seizure types: myoclonic, absence, and generalized tonic-clonic (GTC). In this retrospective study, we analyzed seizure outcome in patients with JME using valproate monotherapy for a minimum period of one year. Low valproate dose was considered to be 1000 mg/day or lower, while serum levels were considered to be low if they were at or below 50 mcg/dl. One hundred three patients met the inclusion criteria. Fifty-six patients (54.4%) were female. The current average age was 28.4 ± 7.4 years, while the age of epilepsy onset was 13.6 ± 2.9 years. Most patients corresponded to the subsyndrome of classic JME. Forty-six (44.7%) patients were free from all seizure types, and 76 (73.7%) patients were free from GTC seizures. No significant difference was found in seizure freedom among patients using a low dose of valproate versus a high dose (p=0.535), or among patients with low blood levels versus high blood levels (p=0.69). In patients with JME, it seems appropriate to use low doses of valproate (500 mg to 1,000 mg) for initial treatment and to evaluate to determine if freedom from seizures was attained.

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Section: Methodsmentioning

confidence: 99%

High-dose versus low-dose valproate for the treatment of juvenile myoclonic epilepsy: Going from low to high

Hernández-Vanegas

Jara‐Prado

Ochoa

et al. 2016

Epilepsy & Behavior

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“…However, mutations in another epilepsy gene (EF-hand domain containing protein 1) have been found in multiple GGE kindreds and, importantly, the penetrance of EFHC1 mutations is less than 100%. We quantified the number of affected and unaffected male and female GGE patients who possessed disruptive EFHC1 mutations that were identified in four different familial studies (Annesi et al, 2007; Jara-Prado et al, 2012; Suzuki et al, 2004, Medina et al, 2008). We found that of the patients that possessed EFHC1 mutations, 24/42 females (57%) and 15/36 males (42%) expressed a GGE syndrome whereas the remainder lacked a discernable phenotype, or simply exhibited childhood febrile seizures, or an asymptomatic abnormal EEG.…”

Section: Human Syndromes With Absence Seizures: Sex Differences?mentioning

confidence: 99%

Animal models of absence epilepsies: What do they model and do sex and sex hormones matter?

Luijtelaar

Onat

Gallagher

2014

Neurobiology of Disease

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While epidemiological data suggest a female prevalence in human childhood- and adolescence-onset typical absence epilepsy syndromes, the sex difference is less clear in adult-onset syndromes. In addition, although there are more females than males diagnosed with typical absence epilepsy syndromes, there is a paucity of studies on sex differences in seizure frequency and semiology in patients diagnosed with any absence epilepsy syndrome. Moreover, it is unknown if there are sex differences in the prevalence or expression of atypical absence epilepsy syndromes. Surprisingly, most studies of animal models of absence epilepsy either did not investigate sex differences, or failed to find sex-dependent effects. However, various rodent models for atypical syndromes such as the AY9944 model (prepubertal females show a higher incidence than prepubertal males), BN model also with a higher prevalence in males and the Gabra1 deletion mouse in the C57BL/6J strain offer unique possibilities for the investigation of the mechanisms involved in sex differences. Although the mechanistic bases for the sex differences in humans or these three models are not yet known, studies of the effects of sex hormones on seizures have offered some possibilities. The sex hormones progesterone, estradiol and testosterone exert diametrically opposite effects in genetic absence epilepsy and pharmacologically-evoked convulsive types of epilepsy models. In addition, acute pharmacological effects of progesterone on absence seizures during proestrus are opposite to those seen during pregnancy. 17β-Estradiol has anti-absence seizure effects, but it is only active in atypical absence models. It is speculated that the pro-absence action of progesterone, and perhaps also the delayed pro-absence action of testosterone, are mediated through the neurosteroid allopregnanolone and its structural and functional homolog, androstanediol. These two steroids increase extrasynaptic thalamic tonic GABAergic inhibition by selectively targeting neurosteroid-selective subunits of GABAA receptors (GABAARs). Neurosteroids also modulate the expression of GABAAR containing the γ2, α4, and δ subunits. It is hypothesized that differences in subunit expression during pregnancy and ovarian cycle contribute to the opposite effects of progesterone in these two hormonal states.

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“…14), were not available in 2004 when variants of the EF-hand domain (C-terminal) containing 1 gene (EFHC1) were reported as disease-causing mutations in myoclonic and grand mal clonic-tonic-clonic (CTC) convulsions produced by juvenile myoclonic epilepsy (JME). Consequently, all EFHC1 variants discovered in the first decade of this millennium and reported with respect to epilepsy or not [15][16][17][18][19][20][21][22][23][24][25][26][27][28] have not been "vetted" through NHGRI and ACMG guidelines. More importantly, both NHGRI and ACMG guidelines advise that "with evidence on variants evolving" and the "content of sequencing tests expanding, " "rigorous evaluation" and "reanalysis of variants are encouraged" to prevent misannotation of the pathogenicity of variants in public databases.…”

mentioning

confidence: 99%

EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality

Bailey

Patterson

Nijs

et al. 2017

Genetics in Medicine

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Novel Myoclonin1/EFHC1 mutations in Mexican patients with juvenile myoclonic epilepsy

Abstract: The frequency of Myoclonin1/EFHC1 mutations in our sample is 7.3%. Thus, we conclude that mutations in the Myoclonin1/EFHC1 gene are an important cause of JME in Mexican patients.

Cited by 21 publications

References 14 publications

High-dose versus low-dose valproate for the treatment of juvenile myoclonic epilepsy: Going from low to high

High-dose versus low-dose valproate for the treatment of juvenile myoclonic epilepsy: Going from low to high

Animal models of absence epilepsies: What do they model and do sex and sex hormones matter?

EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality

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