Phenotypic spectrum of GABRA1: From generalized epilepsies to severe epileptic encephalopathies

Katrine Johannesen, Carla Marini, Siona Pfeffer, Rikke S Møller, Thomas Dorn, Christina Niturad, Elena Gardella, Yvonne Weber, Marianne Søndergård, Helle Hjalgrim, Mariana Nikanorova, Felicitas Becker, Line H G Larsen, Hans A Dahl, Oliver Maier, Davide Mei, Saskia Biskup, Karl M Klein, Philipp S Reif, Felix RosenowAbdallah F Elias, Cindy Hudson, Katherine L Helbig, Susanne Schubert-Bast, Maria R Scordo, Dana Craiu, Tania Djémié, Dorota Hoffman-Zacharska, Hande Caglayan, Ingo Helbig, Jose Serratosa, Pasquale Striano, Peter De Jonghe, Sarah Weckhuysen, Arvid Suls, Kai Muru, Inga Talvik, Tiina Talvik, Hiltrud Muhle, Ingo Borggraefe, Imma Rost, Renzo Guerrini, Holger Lerche, Johannes R Lemke, Guido Rubboli, Snezana Maljevic

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

OBJECTIVE: To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations.

METHODS: Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analysis of 4 selected mutations was performed using the Xenopus laevis oocyte expression system.

RESULTS: The study included 16 novel probands and 3 additional family members with a disease-causing mutation in the GABRA1 gene. The phenotypic spectrum varied from unspecified epilepsy (1), juvenile myoclonic epilepsy (2), photosensitive idiopathic generalized epilepsy (1), and generalized epilepsy with febrile seizures plus (1) to severe epileptic encephalopathies (11). In the epileptic encephalopathy group, the patients had seizures beginning between the first day of life and 15 months, with a mean of 7 months. Predominant seizure types in all patients were tonic-clonic in 9 participants (56%) and myoclonic seizures in 5 (31%). EEG showed a generalized photoparoxysmal response in 6 patients (37%). Four selected mutations studied functionally revealed a loss of function, without a clear genotype-phenotype correlation.

CONCLUSIONS: GABRA1 mutations make a significant contribution to the genetic etiology of both benign and severe epilepsy syndromes. Myoclonic and tonic-clonic seizures with pathologic response to photic stimulation are common and shared features in both mild and severe phenotypes.

OriginalsprogEngelsk
TidsskriftNeurology
Vol/bind87
Udgave nummer11
Sider (fra-til)1140-1151
ISSN0028-3878
DOI
StatusUdgivet - 2016

Fingeraftryk

Mutation
Electroencephalography
Juvenile Myoclonic Epilepsy
Photic Stimulation
Xenopus laevis
Genetic Association Studies
Oocytes

Citer dette

Johannesen, Katrine ; Marini, Carla ; Pfeffer, Siona ; Møller, Rikke S ; Dorn, Thomas ; Niturad, Christina ; Gardella, Elena ; Weber, Yvonne ; Søndergård, Marianne ; Hjalgrim, Helle ; Nikanorova, Mariana ; Becker, Felicitas ; Larsen, Line H G ; Dahl, Hans A ; Maier, Oliver ; Mei, Davide ; Biskup, Saskia ; Klein, Karl M ; Reif, Philipp S ; Rosenow, Felix ; Elias, Abdallah F ; Hudson, Cindy ; Helbig, Katherine L ; Schubert-Bast, Susanne ; Scordo, Maria R ; Craiu, Dana ; Djémié, Tania ; Hoffman-Zacharska, Dorota ; Caglayan, Hande ; Helbig, Ingo ; Serratosa, Jose ; Striano, Pasquale ; De Jonghe, Peter ; Weckhuysen, Sarah ; Suls, Arvid ; Muru, Kai ; Talvik, Inga ; Talvik, Tiina ; Muhle, Hiltrud ; Borggraefe, Ingo ; Rost, Imma ; Guerrini, Renzo ; Lerche, Holger ; Lemke, Johannes R ; Rubboli, Guido ; Maljevic, Snezana. / Phenotypic spectrum of GABRA1 : From generalized epilepsies to severe epileptic encephalopathies. I: Neurology. 2016 ; Bind 87, Nr. 11. s. 1140-1151.
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title = "Phenotypic spectrum of GABRA1: From generalized epilepsies to severe epileptic encephalopathies",
abstract = "OBJECTIVE: To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations.METHODS: Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analysis of 4 selected mutations was performed using the Xenopus laevis oocyte expression system.RESULTS: The study included 16 novel probands and 3 additional family members with a disease-causing mutation in the GABRA1 gene. The phenotypic spectrum varied from unspecified epilepsy (1), juvenile myoclonic epilepsy (2), photosensitive idiopathic generalized epilepsy (1), and generalized epilepsy with febrile seizures plus (1) to severe epileptic encephalopathies (11). In the epileptic encephalopathy group, the patients had seizures beginning between the first day of life and 15 months, with a mean of 7 months. Predominant seizure types in all patients were tonic-clonic in 9 participants (56{\%}) and myoclonic seizures in 5 (31{\%}). EEG showed a generalized photoparoxysmal response in 6 patients (37{\%}). Four selected mutations studied functionally revealed a loss of function, without a clear genotype-phenotype correlation.CONCLUSIONS: GABRA1 mutations make a significant contribution to the genetic etiology of both benign and severe epilepsy syndromes. Myoclonic and tonic-clonic seizures with pathologic response to photic stimulation are common and shared features in both mild and severe phenotypes.",
keywords = "Journal Article",
author = "Katrine Johannesen and Carla Marini and Siona Pfeffer and M{\o}ller, {Rikke S} and Thomas Dorn and Christina Niturad and Elena Gardella and Yvonne Weber and Marianne S{\o}nderg{\aa}rd and Helle Hjalgrim and Mariana Nikanorova and Felicitas Becker and Larsen, {Line H G} and Dahl, {Hans A} and Oliver Maier and Davide Mei and Saskia Biskup and Klein, {Karl M} and Reif, {Philipp S} and Felix Rosenow and Elias, {Abdallah F} and Cindy Hudson and Helbig, {Katherine L} and Susanne Schubert-Bast and Scordo, {Maria R} and Dana Craiu and Tania Dj{\'e}mi{\'e} and Dorota Hoffman-Zacharska and Hande Caglayan and Ingo Helbig and Jose Serratosa and Pasquale Striano and {De Jonghe}, Peter and Sarah Weckhuysen and Arvid Suls and Kai Muru and Inga Talvik and Tiina Talvik and Hiltrud Muhle and Ingo Borggraefe and Imma Rost and Renzo Guerrini and Holger Lerche and Lemke, {Johannes R} and Guido Rubboli and Snezana Maljevic",
note = "{\circledC} 2016 American Academy of Neurology.",
year = "2016",
doi = "10.1212/WNL.0000000000003087",
language = "English",
volume = "87",
pages = "1140--1151",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams & Wilkins",
number = "11",

}

Johannesen, K, Marini, C, Pfeffer, S, Møller, RS, Dorn, T, Niturad, C, Gardella, E, Weber, Y, Søndergård, M, Hjalgrim, H, Nikanorova, M, Becker, F, Larsen, LHG, Dahl, HA, Maier, O, Mei, D, Biskup, S, Klein, KM, Reif, PS, Rosenow, F, Elias, AF, Hudson, C, Helbig, KL, Schubert-Bast, S, Scordo, MR, Craiu, D, Djémié, T, Hoffman-Zacharska, D, Caglayan, H, Helbig, I, Serratosa, J, Striano, P, De Jonghe, P, Weckhuysen, S, Suls, A, Muru, K, Talvik, I, Talvik, T, Muhle, H, Borggraefe, I, Rost, I, Guerrini, R, Lerche, H, Lemke, JR, Rubboli, G & Maljevic, S 2016, 'Phenotypic spectrum of GABRA1: From generalized epilepsies to severe epileptic encephalopathies', Neurology, bind 87, nr. 11, s. 1140-1151. https://doi.org/10.1212/WNL.0000000000003087

Phenotypic spectrum of GABRA1 : From generalized epilepsies to severe epileptic encephalopathies. / Johannesen, Katrine; Marini, Carla; Pfeffer, Siona; Møller, Rikke S; Dorn, Thomas; Niturad, Christina; Gardella, Elena; Weber, Yvonne; Søndergård, Marianne; Hjalgrim, Helle; Nikanorova, Mariana; Becker, Felicitas; Larsen, Line H G; Dahl, Hans A; Maier, Oliver; Mei, Davide; Biskup, Saskia; Klein, Karl M; Reif, Philipp S; Rosenow, Felix; Elias, Abdallah F; Hudson, Cindy; Helbig, Katherine L; Schubert-Bast, Susanne; Scordo, Maria R; Craiu, Dana; Djémié, Tania; Hoffman-Zacharska, Dorota; Caglayan, Hande; Helbig, Ingo; Serratosa, Jose; Striano, Pasquale; De Jonghe, Peter; Weckhuysen, Sarah; Suls, Arvid; Muru, Kai; Talvik, Inga; Talvik, Tiina; Muhle, Hiltrud; Borggraefe, Ingo; Rost, Imma; Guerrini, Renzo; Lerche, Holger; Lemke, Johannes R; Rubboli, Guido; Maljevic, Snezana.

I: Neurology, Bind 87, Nr. 11, 2016, s. 1140-1151.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Phenotypic spectrum of GABRA1

T2 - From generalized epilepsies to severe epileptic encephalopathies

AU - Johannesen, Katrine

AU - Marini, Carla

AU - Pfeffer, Siona

AU - Møller, Rikke S

AU - Dorn, Thomas

AU - Niturad, Christina

AU - Gardella, Elena

AU - Weber, Yvonne

AU - Søndergård, Marianne

AU - Hjalgrim, Helle

AU - Nikanorova, Mariana

AU - Becker, Felicitas

AU - Larsen, Line H G

AU - Dahl, Hans A

AU - Maier, Oliver

AU - Mei, Davide

AU - Biskup, Saskia

AU - Klein, Karl M

AU - Reif, Philipp S

AU - Rosenow, Felix

AU - Elias, Abdallah F

AU - Hudson, Cindy

AU - Helbig, Katherine L

AU - Schubert-Bast, Susanne

AU - Scordo, Maria R

AU - Craiu, Dana

AU - Djémié, Tania

AU - Hoffman-Zacharska, Dorota

AU - Caglayan, Hande

AU - Helbig, Ingo

AU - Serratosa, Jose

AU - Striano, Pasquale

AU - De Jonghe, Peter

AU - Weckhuysen, Sarah

AU - Suls, Arvid

AU - Muru, Kai

AU - Talvik, Inga

AU - Talvik, Tiina

AU - Muhle, Hiltrud

AU - Borggraefe, Ingo

AU - Rost, Imma

AU - Guerrini, Renzo

AU - Lerche, Holger

AU - Lemke, Johannes R

AU - Rubboli, Guido

AU - Maljevic, Snezana

N1 - © 2016 American Academy of Neurology.

PY - 2016

Y1 - 2016

N2 - OBJECTIVE: To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations.METHODS: Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analysis of 4 selected mutations was performed using the Xenopus laevis oocyte expression system.RESULTS: The study included 16 novel probands and 3 additional family members with a disease-causing mutation in the GABRA1 gene. The phenotypic spectrum varied from unspecified epilepsy (1), juvenile myoclonic epilepsy (2), photosensitive idiopathic generalized epilepsy (1), and generalized epilepsy with febrile seizures plus (1) to severe epileptic encephalopathies (11). In the epileptic encephalopathy group, the patients had seizures beginning between the first day of life and 15 months, with a mean of 7 months. Predominant seizure types in all patients were tonic-clonic in 9 participants (56%) and myoclonic seizures in 5 (31%). EEG showed a generalized photoparoxysmal response in 6 patients (37%). Four selected mutations studied functionally revealed a loss of function, without a clear genotype-phenotype correlation.CONCLUSIONS: GABRA1 mutations make a significant contribution to the genetic etiology of both benign and severe epilepsy syndromes. Myoclonic and tonic-clonic seizures with pathologic response to photic stimulation are common and shared features in both mild and severe phenotypes.

AB - OBJECTIVE: To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations.METHODS: Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analysis of 4 selected mutations was performed using the Xenopus laevis oocyte expression system.RESULTS: The study included 16 novel probands and 3 additional family members with a disease-causing mutation in the GABRA1 gene. The phenotypic spectrum varied from unspecified epilepsy (1), juvenile myoclonic epilepsy (2), photosensitive idiopathic generalized epilepsy (1), and generalized epilepsy with febrile seizures plus (1) to severe epileptic encephalopathies (11). In the epileptic encephalopathy group, the patients had seizures beginning between the first day of life and 15 months, with a mean of 7 months. Predominant seizure types in all patients were tonic-clonic in 9 participants (56%) and myoclonic seizures in 5 (31%). EEG showed a generalized photoparoxysmal response in 6 patients (37%). Four selected mutations studied functionally revealed a loss of function, without a clear genotype-phenotype correlation.CONCLUSIONS: GABRA1 mutations make a significant contribution to the genetic etiology of both benign and severe epilepsy syndromes. Myoclonic and tonic-clonic seizures with pathologic response to photic stimulation are common and shared features in both mild and severe phenotypes.

KW - Journal Article

U2 - 10.1212/WNL.0000000000003087

DO - 10.1212/WNL.0000000000003087

M3 - Journal article

C2 - 27521439

VL - 87

SP - 1140

EP - 1151

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 11

ER -