Exome sequencing in 57 patients with self-limited focal epilepsies of childhood with typical or atypical presentations suggests novel candidate genes

Rudolf, Gabrielle; Bellescize, Julitta de; Saint‐Martin, Anne de; Arzimanoglou, Alexis; Hirsch, Maria Paola Valenti; Labalme, Audrey; Boulay, Clotilde; Simonet, Thomas; Boland, Anne; Deleuze, Jean; Nitschké, Patrick; Ollivier, Emmanuelle; Sanlaville, Damien; Hirsch, Édouard; Chelly, Jamel; Lesca, Gaëtan

doi:10.1016/j.ejpn.2020.05.003

Cited by 20 publications

(16 citation statements)

References 54 publications

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“…542, Gene Panel for Monogenic Epilepsies). Genetic diagnosis was performed using next-generation sequencing (exome sequencing for patient 1 and gene panel for patient 2), as described ( 53 ).…”

Section: Methodsmentioning

confidence: 99%

Gain of function due to increased opening probability by two KCNQ5 pore variants causing developmental and epileptic encephalopathy

Nappi

Barrese

Carotenuto

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance Variants in genes encoding neuronally expressed potassium channel subunits are frequent causes of developmental and epileptic encephalopathies (DEEs). Characterization of their functional consequences is critical to confirm diagnosis, assess prognosis, and implement personalized treatments. In the present work, we describe two patients carrying variants in KCNQ5 , a gene very recently and rarely found involved in DEEs, and reveal that they both cause remarkable gain-of-function consequences on channel activity. A PIP 2 -independent increase in open probability, without effects on membrane abundance or single-channel conductance, was responsible for the observed mutation-induced functional changes, thus revealing a pathomolecular disease mechanism for DEEs.

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Section: Methodsmentioning

confidence: 99%

Gain of function due to increased opening probability by two KCNQ5 pore variants causing developmental and epileptic encephalopathy

Nappi

Barrese

Carotenuto

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…Because of the family history of behavioral and developmental disorders among the parents’ couples and the shared clinical and instrumental characteristics among the daughters, we obviously firstly supposed a common genetic background in this family. In particular, we supposed a causative role of GRIN2A gene, that recently emerged as the major candidate for the SeLFE syndromes with an uncommon presentation and a variable prognosis [11] , [12] , [14] . However, the lack of significant results in the genetic analysis by NGS did not confirm our hypothesis.…”

Section: Discussionmentioning

confidence: 99%

A peculiar family with recurrent self-limited epileptic syndrome and associated developmental disorders in six girls

Cursio

Ronzano

Asunis

et al. 2022

Epilepsy & Behavior Reports

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“…RE and related syndromes with atypical features do not follow a Mendelian inheritance mode [43]. The clinical and genetic studies have shown complex inheritance [43][44][45][46][47][48][49][50][51].…”

Section: Etiologymentioning

confidence: 99%

Rolandic Epilepsy: Self-Limited Epilepsy with Centrotemporal Spikes

Guliyeva¹,

Tatishvili²,

Kaiyrzhanov³

2021

Epilepsy - Update on Classification, Etiologies, Instrumental Diagnosis and Treatment

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Childhood epilepsy with centrotemporal spikes, had been previously considered as benign childhood epilepsy. According to the new classification proposed by Sheffer I. and colleagues the term “benign” has been changed to “self-limited”. Many studies reported that BECTS may cause transient or long lasting cognitive and behavioral disturbances. Rolandic epilepsy is the most frequent among the childhood focal epilepsy and may account for about 15–25% of all epileptic syndromes diagnosed between the ages of 5 to 15 years. The incidence range changes between 7.1–21 per 100000 in population younger than 15 years with male predominance. The age of onset in 90% of cases between 1 and 10 years with peak around 6–7 years. Seizures mainly occur during a night sleep, whereas the probability of awake seizures are less than 10%. The characteristic clinical features are: (1) focal motor seizure with unilateral orofacial tonic or clonic contractions; (2) speech arrest; (3) hypersalivation; (4) sensory symptoms represented by unilateral numbness or paresthesia of tongue, lips, gum and inner part of the check; (5) unilateral clonic jerk in leg and arm with postictal paresis; (6) generalized seizures. The EEG picture is distinctive in Rolandic epilepsy. The background activity is almost always preserved in awake state and during a sleep. The typical interictal EEG pattern is high voltage, diphasic spikes or sharp waves frequently with slow activity on central-midtemporal region. The centrotemporal spikes or rolandic spikes come from the lower rolandic region created a horizontal dipole with maximal electronegativity in the centrotemporal region and electropositivity in the frontal region usually seen unilateral or bilateral. In most cases children with RE have a good prognosis regarding both seizures and neurodevelopment. The remission of seizures usually occurs before the age of 18 years. The cognitive and behavior problem may happen in active period of disease which are reversable in most of patients.

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Exome sequencing in 57 patients with self-limited focal epilepsies of childhood with typical or atypical presentations suggests novel candidate genes

Cited by 20 publications

References 54 publications

Gain of function due to increased opening probability by two KCNQ5 pore variants causing developmental and epileptic encephalopathy

Gain of function due to increased opening probability by two KCNQ5 pore variants causing developmental and epileptic encephalopathy

A peculiar family with recurrent self-limited epileptic syndrome and associated developmental disorders in six girls

Rolandic Epilepsy: Self-Limited Epilepsy with Centrotemporal Spikes

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