121 research outputs found
<i>GRIN2A</i>-related disorders:genotype and functional consequence predict phenotype
Alterations of the N-methyl-d-aspartate receptor (NMDAR) subunit GluN2A, encoded by GRIN2A, have been associated with a spectrum of neurodevelopmental disorders with prominent speech-related features, and epilepsy. We performed a comprehensive assessment of phenotypes with a standardized questionnaire in 92 previously unreported individuals with GRIN2A-related disorders. Applying the criteria of the American College of Medical Genetics and Genomics to all published variants yielded 156 additional cases with pathogenic or likely pathogenic variants in GRIN2A, resulting in a total of 248 individuals. The phenotypic spectrum ranged from normal or near-normal development with mild epilepsy and speech delay/apraxia to severe developmental and epileptic encephalopathy, often within the epilepsy-aphasia spectrum. We found that pathogenic missense variants in transmembrane and linker domains (misTMD+Linker) were associated with severe developmental phenotypes, whereas missense variants within amino terminal or ligand-binding domains (misATD+LBD) and null variants led to less severe developmental phenotypes, which we confirmed in a discovery (P = 10-6) as well as validation cohort (P = 0.0003). Other phenotypes such as MRI abnormalities and epilepsy types were also significantly different between the two groups. Notably, this was paralleled by electrophysiology data, where misTMD+Linker predominantly led to NMDAR gain-of-function, while misATD+LBD exclusively caused NMDAR loss-of-function. With respect to null variants, we show that Grin2a+/- cortical rat neurons also had reduced NMDAR function and there was no evidence of previously postulated compensatory overexpression of GluN2B. We demonstrate that null variants and misATD+LBD of GRIN2A do not only share the same clinical spectrum (i.e. milder phenotypes), but also result in similar electrophysiological consequences (loss-of-function) opposing those of misTMD+Linker (severe phenotypes; predominantly gain-of-function). This new pathomechanistic model may ultimately help in predicting phenotype severity as well as eligibility for potential precision medicine approaches in GRIN2A-related disorders
Spacil (Theophilus), Doctrina theologiæ Orienlis separati de Revelatione, Fide, Dogmate. Pars altera : Doctrina theologiae Orientis separati examinatur
Serraz L. Spacil (Theophilus), Doctrina theologiæ Orienlis separati de Revelatione, Fide, Dogmate. Pars altera : Doctrina theologiae Orientis separati examinatur. In: Échos d'Orient, tome 35, n°182, 1936. pp. 254-255
Nematallah Carame (Mgr), Avicennae Metaphysices compendium ex arabo latinum reddidit
Serraz L. Nematallah Carame (Mgr), Avicennae Metaphysices compendium ex arabo latinum reddidit. In: Échos d'Orient, tome 26, n°147, 1927. pp. 377-378
Batiffol (M. Pierre), Catholicisme et papauté. Les difficultés anglicanes et russes.
Serraz L. Batiffol (M. Pierre), Catholicisme et papauté. Les difficultés anglicanes et russes.. In: Échos d'Orient, tome 26, n°145, 1927. pp. 125-126
Spacil (Theophilus), Doctrina theologiæ Orienlis separati de Revelatione, Fide, Dogmate. Pars altera : Doctrina theologiae Orientis separati examinatur
Serraz L. Spacil (Theophilus), Doctrina theologiæ Orienlis separati de Revelatione, Fide, Dogmate. Pars altera : Doctrina theologiae Orientis separati examinatur. In: Échos d'Orient, tome 35, n°182, 1936. pp. 254-255
Svoboda (K.) La démonologie de Michel Psellos
Serraz L. Svoboda (K.) La démonologie de Michel Psellos. In: Échos d'Orient, tome 28, n°153, 1929. p. 119
M.-J. Lagrange, Ο. P., Saint Paul, Épitre aux Galates; Évangile selon saint Marc ; Évangile selon saint Luc ; Épitre aux Romains ; Saint Matthieu.
Serraz L. M.-J. Lagrange, Ο. P., Saint Paul, Épitre aux Galates; Évangile selon saint Marc ; Évangile selon saint Luc ; Épitre aux Romains ; Saint Matthieu.. In: Échos d'Orient, tome 25, n°142, 1926. pp. 244-248
Otto Bardenhewer, Geschichte der altkirchlichen Literatur.IVe volume : Das fünfte Jahrhundert mit Einschluss der Syrischen Literatur des vierten Jahrhunderts
Serraz L. Otto Bardenhewer, Geschichte der altkirchlichen Literatur.IVe volume : Das fünfte Jahrhundert mit Einschluss der Syrischen Literatur des vierten Jahrhunderts. In: Échos d'Orient, tome 25, n°143, 1926. p. 376
Laskaris, M., Vizantiske princese y srednje vekovnoj Srbiji.
Serraz L. Laskaris, M., Vizantiske princese y srednje vekovnoj Srbiji.. In: Échos d'Orient, tome 28, n°155, 1929. p. 384
Renauld (Emile), Michel Psellos. Chronographie ou Histoire d'un siècle de Byzance (976-1077), t. I, texte établi et traduit
Serraz L. Renauld (Emile), Michel Psellos. Chronographie ou Histoire d'un siècle de Byzance (976-1077), t. I, texte établi et traduit. In: Échos d'Orient, tome 26, n°148, 1927. pp. 502-503
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