A new molecular mechanism for severe myoclonic epilepsy of infancy: Exonic deletions in
            <i>SCN1A</i>

Mulley, John C.; Nelson, Paul V.; Guerrero, Sílvia; Dibbens, Leanne M.; Iona, Xenia; McMahon, Jacinta M.; Harkin, Louise A.; Schouten, Jan P.; Yu, Shaohua; Berkovic, Samuel F.; Scheffer, Ingrid E.

doi:10.1212/01.wnl.0000237322.04338.2b

Cited by 95 publications

(87 citation statements)

References 7 publications

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“…SCN1A rearrangements of large fragments were responsible about 10% patients without mutations by PCR-sequencing, in which deletions were more frequent than duplications. 18,19 MLPA analysis was necessary for PCR-sequencing-negative patients, for about 12.5% Analysis of SCN1A mutation and parental origin H Sun et al (2 of 16) were abnormal. There were still 14 DS patients with no SCN1A mutations in our study, other genes such as SCN9A and PCDH19 may be involved in the pathogenesis of DS.…”

Section: Scn1a Mutationmentioning

confidence: 99%

Analysis of SCN1A mutation and parental origin in patients with Dravet syndrome

et al. 2010

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Dravet syndrome (DS) or severe myoclonic epilepsy of infancy is an intractable epileptic syndrome that is caused by mutations in the neuronal voltage-gated sodium channel a1 subunit gene SCN1A. We investigated SCN1A mutations in 63 Chinese patients with DS and analyzed its inheritance. Genomic DNA was extracted from peripheral blood lymphocytes of DS patients and their available parents. The SCN1A open reading frame sequence was analyzed by PCR-DNA sequencing and multiple ligation-dependent probe amplication (MLPA). If the mutation was de novo, we used allele-specific PCR (AS-PCR) to determine the parental origin. Of the 63 patients examined, 49 unrelated patients had SCN1A mutations. The mutation rate was 77.8% (49 of 63), in which 61.2% (30 of 49) were truncation mutations. The mutations included 19 missense mutations, 14 frame-shift mutations, 6 nonsense mutations, 8 splice-site mutations. Through MLPA analysis, deletions or duplications of large fragments accounted for 12.5% (2 of 16) in PCR-sequencing-negative patients. By testing parents for the mutation, 40 mutations were found to be de novo and one mutation was inherited from a mother who was mosaic for a mutation. By AS-PCR analysis in 12 patients with de novo mutations, 10 were confirmed paternal in origin and 2 were maternal in origin. Thirty of the SCN1A mutations reported here have not been previously reported. Approximately 80% of Chinese DS patients have SCN1A mutations. MLPA analysis was essential for PCR-sequencingnegative patients. The majority of SCN1A mutations were de novo, most of which were paternal origin.

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Section: Scn1a Mutationmentioning

confidence: 99%

Analysis of SCN1A mutation and parental origin in patients with Dravet syndrome

et al. 2010

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“…Most mutations in SMEI were de novo: two thirds were truncation, one third were missense mutations, and deletions of large exons were identified in some SMEI (Yamakawa 2006;Mulley et al 2006). Almost all SCN1A mutations in GEFS+ were inherited missense mutations.…”

Section: Scn1a Mutationmentioning

confidence: 99%

SCN1A, SCN1B, and GABRG2 gene mutation analysis in Chinese families with generalized epilepsy with febrile seizures plus

et al. 2008

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Generalized epilepsy with febrile seizures plus (GEFS+; MIM#604233) is a familial epilepsy syndrome characterized by phenotypic and genetic heterogeneity. It was associated with mutations in the neuronal voltagegated sodium channel subunit gene (SCN1A, SCN2A, SCN1B) and ligand-gated gamma aminobutyric acid receptors genes (GABRG2, GABRD). We investigated the roles of SCN1A, SCN1B, and GABRG2 mutations in the etiology of Chinese GEFS+ families. Genomic deoxyribonucleic acid (DNA) was extracted from peripheral blood lymphocytes of 23 probands and their family members. The sequences of SCN1A, SCN1B, and GABRG2 genes were analyzed by polymerase chain reaction (PCR) and direct sequencing. The major phenotypes of affected members in the 23 GEFS+ families exhibited FS and FS+, whereas rare phenotypes afebrile generalized tonic-clonic seizures (AGTCS), myoclonic-astatic epilepsy (MAE), and partial seizures were also observed. A novel SCN1A mutation, p.N935H, was identified in one family and another novel mutation in GABRG2, p.W390X, in another family. However, no SCN1B mutation was identified. The combined frequency of SCN1A, SCN1B, and GABRG2 mutations was 8.7% (2/23), extending the distribution of SCN1A and GABRG2 mutations to Chinese GEFS+ families. There were still unidentified genes contributing to the pathogenesis of GEFS+.

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“…En la mayoría de los casos involucra una mutación de novo del gen del canal de sodio SCN1A 13 , mutación que fue confirmada en los casos presentados.…”

Section: Discussionunclassified

“…La dieta cetogéni-ca, tratamientos no farmacológico igualmente recomendado [11][12][13] , se asoció a pancreatitis en el caso 2. El Stiripentol, droga registrada en Europa, Canadá y Japón, que actúa como modulador alostérico del receptor del ácido gama aminobutírico y recomendada para el SD, no tuvo el efecto antiepilépticos deseado en nuestro paciente (caso 2) con dosis de 40-50 mg kp día asociado a topiramato, ácido valproico y clonazepam 17 .…”

Section: Discussionunclassified

¿Crisis febriles complejas o síndrome de Dravet?: Descripción de 3 casos clínicos

Chávez

Latorre

Herrera³

et al. 2014

Rev. chil. pediatr.

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Complex febrile seizures or Dravet syndrome? Description of 3 case reports introduction: Dravet syndrome (DS) is one of the most intractable forms of epilepsy that begins in infancy. This syndrome is characterized by beginning with complex febrile seizures (FS) in a healthy infant and progresses to refractory epilepsy with psychomotor regression. The detection of a SCN1A mutation encoding the sodium channel can confirm the diagnosis. Objective: To report 3 confirmed cases of genetically DS. Case reports: We describe 3 girls diagnosed with complex FS that started when they were between 2 and 7 months old. FS were frequent, hemi generalized and myoclonic associated with recurrent febrile status epilepticus (SE). Despite FS and SE recurrence, the psychomotor development, electrophysiological studies and magnetic resonance imaging (MRI) of the brain were normal. After a year, they developed afebrile seizures progressing to refractory epilepsy with developmental regression. A molecular study detected SCN1A mutation confirming DS. The specific antiepileptic treatment and prevention of febrile episodes allowed partial control of epilepsy with some recovery of psychomotor skills. Conclusions: The high frequency complex FS associated with recurrent SE in a previously healthy infant should alert about the possibility of DS. Molecular diagnostics helps us to establish a drugs and non-drug therapies treatment, as well as long-term prognosis and genetic counseling. CASOS CLíNICOSRev

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A new molecular mechanism for severe myoclonic epilepsy of infancy: Exonic deletions in SCN1A

Cited by 95 publications

References 7 publications

Analysis of SCN1A mutation and parental origin in patients with Dravet syndrome

Analysis of SCN1A mutation and parental origin in patients with Dravet syndrome

SCN1A, SCN1B, and GABRG2 gene mutation analysis in Chinese families with generalized epilepsy with febrile seizures plus

¿Crisis febriles complejas o síndrome de Dravet?: Descripción de 3 casos clínicos

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