Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants
- Autores
- Neuray, Caroline; Maroofian, Reza; Scala, Marcello; Sultan, Tipu; Pai, Gurpur S.; Mojarrad, Majid; El Khashab, Heba; deHoll, Leigh; Yue, Wyatt; Alsaif, Hessa S.; Zanetti, Maria Natalia; Bello, Oscar Daniel; Person, Richard; Eslahi, Atieh; Khazaei, Zaynab; Feizabadi, Masoumeh H.; Efthymiou, Stephanie; El Bassyouni, Hala T.; Soliman, Doaa R.; Tekes, Selahattin; Ozer, Leyla; Baltaci, Volkan; Khan, Suliman; Beetz, Christian; Amr, Khalda S.; Salpietro, Vincenzo; Jamshidi, Yalda; Alkuraya, Fowzan S.; Houlden, Henry
- Año de publicación
- 2020
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1-/- mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy.
Fil: Neuray, Caroline. University College London; Estados Unidos
Fil: Maroofian, Reza. University College London; Estados Unidos
Fil: Scala, Marcello. University College London; Estados Unidos
Fil: Sultan, Tipu. Children’s Hospital and Institute of Child Health,; Pakistán
Fil: Pai, Gurpur S.. Medical University of South Carolina; Estados Unidos
Fil: Mojarrad, Majid. Mashhad University of Medical Sciences; Irán. Genetic Center of Khorasan Razavi; Irán
Fil: El Khashab, Heba. , Children’s Hospital, Ain Shams University; Egipto
Fil: deHoll, Leigh. Medical University Of South Carolina; Estados Unidos
Fil: Yue, Wyatt. University of Oxford; Reino Unido
Fil: Alsaif, Hessa S.. Mashhad University of Medical Sciences; Irán
Fil: Zanetti, Maria Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. University College London; Estados Unidos
Fil: Bello, Oscar Daniel. University College London; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Person, Richard. No especifíca;
Fil: Eslahi, Atieh. University College London; Estados Unidos
Fil: Khazaei, Zaynab. Genetic Center of Khorasan Razavi; Irán
Fil: Feizabadi, Masoumeh H.. Mashhad University Of Medical Sciences; Irán
Fil: Efthymiou, Stephanie. Colegio Universitario de Londres; Reino Unido
Fil: El Bassyouni, Hala T.. Colegio Universitario de Londres; Reino Unido
Fil: Soliman, Doaa R.. Benha University; Egipto
Fil: Tekes, Selahattin. Dicle University; Turquía
Fil: Ozer, Leyla. Yuksek Ihtisas University; Turquía
Fil: Baltaci, Volkan. Mikrogen Genetic Diagnosis Center; Turquía
Fil: Khan, Suliman. No especifíca;
Fil: Beetz, Christian. No especifíca;
Fil: Amr, Khalda S.. National Research Centre; Egipto
Fil: Salpietro, Vincenzo. University College London; Estados Unidos
Fil: Jamshidi, Yalda. University of London; Reino Unido
Fil: Alkuraya, Fowzan S.. King Faisal Specialist Hospital and Research Center Riyadh; Arabia Saudita
Fil: Houlden, Henry. University of London; Reino Unido - Materia
-
CLEFT PALATE
EPILEPSY
GAD1
MUSCLE WEAKNESS
NEURODEVELOPMENTAL DELAY - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/138749
Ver los metadatos del registro completo
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Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variantsNeuray, CarolineMaroofian, RezaScala, MarcelloSultan, TipuPai, Gurpur S.Mojarrad, MajidEl Khashab, HebadeHoll, LeighYue, WyattAlsaif, Hessa S.Zanetti, Maria NataliaBello, Oscar DanielPerson, RichardEslahi, AtiehKhazaei, ZaynabFeizabadi, Masoumeh H.Efthymiou, StephanieEl Bassyouni, Hala T.Soliman, Doaa R.Tekes, SelahattinOzer, LeylaBaltaci, VolkanKhan, SulimanBeetz, ChristianAmr, Khalda S.Salpietro, VincenzoJamshidi, YaldaAlkuraya, Fowzan S.Houlden, HenryCLEFT PALATEEPILEPSYGAD1MUSCLE WEAKNESSNEURODEVELOPMENTAL DELAYhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1-/- mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy.Fil: Neuray, Caroline. University College London; Estados UnidosFil: Maroofian, Reza. University College London; Estados UnidosFil: Scala, Marcello. University College London; Estados UnidosFil: Sultan, Tipu. Children’s Hospital and Institute of Child Health,; PakistánFil: Pai, Gurpur S.. Medical University of South Carolina; Estados UnidosFil: Mojarrad, Majid. Mashhad University of Medical Sciences; Irán. Genetic Center of Khorasan Razavi; IránFil: El Khashab, Heba. , Children’s Hospital, Ain Shams University; EgiptoFil: deHoll, Leigh. Medical University Of South Carolina; Estados UnidosFil: Yue, Wyatt. University of Oxford; Reino UnidoFil: Alsaif, Hessa S.. Mashhad University of Medical Sciences; IránFil: Zanetti, Maria Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. University College London; Estados UnidosFil: Bello, Oscar Daniel. University College London; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Person, Richard. No especifíca;Fil: Eslahi, Atieh. University College London; Estados UnidosFil: Khazaei, Zaynab. Genetic Center of Khorasan Razavi; IránFil: Feizabadi, Masoumeh H.. Mashhad University Of Medical Sciences; IránFil: Efthymiou, Stephanie. Colegio Universitario de Londres; Reino UnidoFil: El Bassyouni, Hala T.. Colegio Universitario de Londres; Reino UnidoFil: Soliman, Doaa R.. Benha University; EgiptoFil: Tekes, Selahattin. Dicle University; TurquíaFil: Ozer, Leyla. Yuksek Ihtisas University; TurquíaFil: Baltaci, Volkan. Mikrogen Genetic Diagnosis Center; TurquíaFil: Khan, Suliman. No especifíca;Fil: Beetz, Christian. No especifíca;Fil: Amr, Khalda S.. National Research Centre; EgiptoFil: Salpietro, Vincenzo. University College London; Estados UnidosFil: Jamshidi, Yalda. University of London; Reino UnidoFil: Alkuraya, Fowzan S.. King Faisal Specialist Hospital and Research Center Riyadh; Arabia SauditaFil: Houlden, Henry. University of London; Reino UnidoOxford University Press2020-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/138749Neuray, Caroline; Maroofian, Reza; Scala, Marcello; Sultan, Tipu; Pai, Gurpur S.; et al.; Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants; Oxford University Press; Brain; 143; 8; 8-2020; 2388-23970006-8950CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/brain/article/143/8/2388/5875729info:eu-repo/semantics/altIdentifier/doi/10.1093/brain/awaa178info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:18:00Zoai:ri.conicet.gov.ar:11336/138749instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:18:00.834CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants |
| title |
Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants |
| spellingShingle |
Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants Neuray, Caroline CLEFT PALATE EPILEPSY GAD1 MUSCLE WEAKNESS NEURODEVELOPMENTAL DELAY |
| title_short |
Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants |
| title_full |
Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants |
| title_fullStr |
Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants |
| title_full_unstemmed |
Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants |
| title_sort |
Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants |
| dc.creator.none.fl_str_mv |
Neuray, Caroline Maroofian, Reza Scala, Marcello Sultan, Tipu Pai, Gurpur S. Mojarrad, Majid El Khashab, Heba deHoll, Leigh Yue, Wyatt Alsaif, Hessa S. Zanetti, Maria Natalia Bello, Oscar Daniel Person, Richard Eslahi, Atieh Khazaei, Zaynab Feizabadi, Masoumeh H. Efthymiou, Stephanie El Bassyouni, Hala T. Soliman, Doaa R. Tekes, Selahattin Ozer, Leyla Baltaci, Volkan Khan, Suliman Beetz, Christian Amr, Khalda S. Salpietro, Vincenzo Jamshidi, Yalda Alkuraya, Fowzan S. Houlden, Henry |
| author |
Neuray, Caroline |
| author_facet |
Neuray, Caroline Maroofian, Reza Scala, Marcello Sultan, Tipu Pai, Gurpur S. Mojarrad, Majid El Khashab, Heba deHoll, Leigh Yue, Wyatt Alsaif, Hessa S. Zanetti, Maria Natalia Bello, Oscar Daniel Person, Richard Eslahi, Atieh Khazaei, Zaynab Feizabadi, Masoumeh H. Efthymiou, Stephanie El Bassyouni, Hala T. Soliman, Doaa R. Tekes, Selahattin Ozer, Leyla Baltaci, Volkan Khan, Suliman Beetz, Christian Amr, Khalda S. Salpietro, Vincenzo Jamshidi, Yalda Alkuraya, Fowzan S. Houlden, Henry |
| author_role |
author |
| author2 |
Maroofian, Reza Scala, Marcello Sultan, Tipu Pai, Gurpur S. Mojarrad, Majid El Khashab, Heba deHoll, Leigh Yue, Wyatt Alsaif, Hessa S. Zanetti, Maria Natalia Bello, Oscar Daniel Person, Richard Eslahi, Atieh Khazaei, Zaynab Feizabadi, Masoumeh H. Efthymiou, Stephanie El Bassyouni, Hala T. Soliman, Doaa R. Tekes, Selahattin Ozer, Leyla Baltaci, Volkan Khan, Suliman Beetz, Christian Amr, Khalda S. Salpietro, Vincenzo Jamshidi, Yalda Alkuraya, Fowzan S. Houlden, Henry |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
CLEFT PALATE EPILEPSY GAD1 MUSCLE WEAKNESS NEURODEVELOPMENTAL DELAY |
| topic |
CLEFT PALATE EPILEPSY GAD1 MUSCLE WEAKNESS NEURODEVELOPMENTAL DELAY |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1-/- mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy. Fil: Neuray, Caroline. University College London; Estados Unidos Fil: Maroofian, Reza. University College London; Estados Unidos Fil: Scala, Marcello. University College London; Estados Unidos Fil: Sultan, Tipu. Children’s Hospital and Institute of Child Health,; Pakistán Fil: Pai, Gurpur S.. Medical University of South Carolina; Estados Unidos Fil: Mojarrad, Majid. Mashhad University of Medical Sciences; Irán. Genetic Center of Khorasan Razavi; Irán Fil: El Khashab, Heba. , Children’s Hospital, Ain Shams University; Egipto Fil: deHoll, Leigh. Medical University Of South Carolina; Estados Unidos Fil: Yue, Wyatt. University of Oxford; Reino Unido Fil: Alsaif, Hessa S.. Mashhad University of Medical Sciences; Irán Fil: Zanetti, Maria Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. University College London; Estados Unidos Fil: Bello, Oscar Daniel. University College London; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Person, Richard. No especifíca; Fil: Eslahi, Atieh. University College London; Estados Unidos Fil: Khazaei, Zaynab. Genetic Center of Khorasan Razavi; Irán Fil: Feizabadi, Masoumeh H.. Mashhad University Of Medical Sciences; Irán Fil: Efthymiou, Stephanie. Colegio Universitario de Londres; Reino Unido Fil: El Bassyouni, Hala T.. Colegio Universitario de Londres; Reino Unido Fil: Soliman, Doaa R.. Benha University; Egipto Fil: Tekes, Selahattin. Dicle University; Turquía Fil: Ozer, Leyla. Yuksek Ihtisas University; Turquía Fil: Baltaci, Volkan. Mikrogen Genetic Diagnosis Center; Turquía Fil: Khan, Suliman. No especifíca; Fil: Beetz, Christian. No especifíca; Fil: Amr, Khalda S.. National Research Centre; Egipto Fil: Salpietro, Vincenzo. University College London; Estados Unidos Fil: Jamshidi, Yalda. University of London; Reino Unido Fil: Alkuraya, Fowzan S.. King Faisal Specialist Hospital and Research Center Riyadh; Arabia Saudita Fil: Houlden, Henry. University of London; Reino Unido |
| description |
Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1-/- mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020-08 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
| status_str |
publishedVersion |
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http://hdl.handle.net/11336/138749 Neuray, Caroline; Maroofian, Reza; Scala, Marcello; Sultan, Tipu; Pai, Gurpur S.; et al.; Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants; Oxford University Press; Brain; 143; 8; 8-2020; 2388-2397 0006-8950 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/138749 |
| identifier_str_mv |
Neuray, Caroline; Maroofian, Reza; Scala, Marcello; Sultan, Tipu; Pai, Gurpur S.; et al.; Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants; Oxford University Press; Brain; 143; 8; 8-2020; 2388-2397 0006-8950 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
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info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/brain/article/143/8/2388/5875729 info:eu-repo/semantics/altIdentifier/doi/10.1093/brain/awaa178 |
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Oxford University Press |
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Oxford University Press |
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