Show simple item record

dc.contributor.authorLabalme, Audrey
dc.contributor.authorTÜYSÜZ, Beyhan
dc.contributor.authorRoselli, Sandra
dc.contributor.authorNajafi, Maryam
dc.contributor.authorULUDAĞ ALKAYA, Dilek
dc.contributor.authorAshrafzadeh, Farah
dc.contributor.authorNabil, Amira
dc.contributor.authorOmar, Tarek
dc.contributor.authorMaroofian, Reza
dc.contributor.authorHussien, Haytham
dc.contributor.authorKok, Fernando
dc.contributor.authorRamos, Luiza
dc.contributor.authorGunes, Nilay
dc.contributor.authorBilguvar, Kaya
dc.contributor.authorHardies, Katia
dc.contributor.authorAlix, Eudeline
dc.contributor.authorSanlaville, Damien
dc.contributor.authorde Bellescize, Julitta
dc.contributor.authorPoulat, Anne-Lise
dc.contributor.authorMoslemi, Ali-Reza
dc.contributor.authorLerche, Holger
dc.contributor.authorMay, Patrick
dc.contributor.authorLesca, Gaetan
dc.contributor.authorWeckhuysen, Sarah
dc.contributor.authorTajsharghi, Homa
dc.contributor.authorKarimiani, Ehsan Ghayoor
dc.contributor.authorChatron, Nicolas
dc.contributor.authorBecker, Felicitas
dc.contributor.authorMorsy, Heba
dc.contributor.authorSchmidts, Miriam
dc.date.accessioned2021-03-02T18:31:07Z
dc.date.available2021-03-02T18:31:07Z
dc.identifier.citationChatron N., Becker F., Morsy H., Schmidts M., Hardies K., TÜYSÜZ B., Roselli S., Najafi M., ULUDAĞ ALKAYA D., Ashrafzadeh F., et al., "Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy", BRAIN, cilt.143, ss.1447-1461, 2020
dc.identifier.issn0006-8950
dc.identifier.otherav_4ab080c6-b722-4a5f-b4fb-d8b8f60e3cd5
dc.identifier.othervv_1032021
dc.identifier.urihttp://hdl.handle.net/20.500.12627/5066
dc.identifier.urihttps://doi.org/10.1093/brain/awaa085
dc.description.abstractDevelopmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1(-/-) mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the c-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele.
dc.language.isoeng
dc.subjectSağlık Bilimleri
dc.subjectDahili Tıp Bilimleri
dc.subjectNöroloji
dc.subjectYaşam Bilimleri
dc.subjectTemel Bilimler
dc.subjectYaşam Bilimleri (LIFE)
dc.subjectTıp
dc.subjectSinirbilim ve Davranış
dc.subjectKLİNİK NEUROLOJİ
dc.subjectKlinik Tıp
dc.subjectKlinik Tıp (MED)
dc.subjectNEUROSCIENCES
dc.titleBi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy
dc.typeMakale
dc.relation.journalBRAIN
dc.contributor.departmentSt Georges University London , ,
dc.identifier.volume143
dc.identifier.startpage1447
dc.identifier.endpage1461
dc.contributor.firstauthorID2281833


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record