Clinical and molecular characterization of patients with YWHAG-related epilepsy
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Clinical and molecular characterization of patients with YWHAG-related epilepsy. / Cetica, Valentina; Pisano, Tiziana; Lesca, Gaetan; Marafi, Dana; Licchetta, Laura; Riccardi, Florence; Mei, Davide; Chung, Hon yin B.; Bayat, Allan; Balasubramanian, Meena; Lowenstein, Daniel H.; Endzinienė, Milda; Alotaibi, Maha; Villeneuve, Nathalie; Jacobs, Julia; Isidor, Bertrand; Solazzi, Roberta; den Hollander, Nicolette S.; Marjanovic, Dragan; Rougeot-Jung, Christelle; Jung, Julien; Lesieur-Sebellin, Marion; Accogli, Andrea; Salpietro, Vincenzo; Saadi, Nebal W.; Panagiotakaki, Eleni; Foiadelli, Thomas; Redon, Sylvia; Tsai, Meng Han; Bisulli, Francesca; Hammer, Trine B.; Lupski, James R.; Parrini, Elena; Guerrini, Renzo.
I: Epilepsia, Bind 65, Nr. 5, 2024, s. 1439-1450.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Clinical and molecular characterization of patients with YWHAG-related epilepsy
AU - Cetica, Valentina
AU - Pisano, Tiziana
AU - Lesca, Gaetan
AU - Marafi, Dana
AU - Licchetta, Laura
AU - Riccardi, Florence
AU - Mei, Davide
AU - Chung, Hon yin B.
AU - Bayat, Allan
AU - Balasubramanian, Meena
AU - Lowenstein, Daniel H.
AU - Endzinienė, Milda
AU - Alotaibi, Maha
AU - Villeneuve, Nathalie
AU - Jacobs, Julia
AU - Isidor, Bertrand
AU - Solazzi, Roberta
AU - den Hollander, Nicolette S.
AU - Marjanovic, Dragan
AU - Rougeot-Jung, Christelle
AU - Jung, Julien
AU - Lesieur-Sebellin, Marion
AU - Accogli, Andrea
AU - Salpietro, Vincenzo
AU - Saadi, Nebal W.
AU - Panagiotakaki, Eleni
AU - Foiadelli, Thomas
AU - Redon, Sylvia
AU - Tsai, Meng Han
AU - Bisulli, Francesca
AU - Hammer, Trine B.
AU - Lupski, James R.
AU - Parrini, Elena
AU - Guerrini, Renzo
N1 - Publisher Copyright: © 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
PY - 2024
Y1 - 2024
N2 - Objective: YWHAG variant alleles have been associated with a rare disease trait whose clinical synopsis includes an early onset epileptic encephalopathy with predominantly myoclonic seizures, developmental delay/intellectual disability, and facial dysmorphisms. Through description of a large cohort, which doubles the number of reported patients, we further delineate the spectrum of YWHAG-related epilepsy. Methods: We included in this study 24 patients, 21 new and three previously described, with pathogenic/likely pathogenic variants in YWHAG. We extended the analysis of clinical, electroencephalographic, brain magnetic resonance imaging, and molecular genetic information to 24 previously published patients. Results: The phenotypic spectrum of YWHAG-related disorders ranges from mild developmental delay to developmental and epileptic encephalopathy (DEE). Epilepsy onset is in the first 2 years of life. Seizure freedom can be achieved in half of the patients (13/24, 54%). Intellectual disability (23/24, 96%), behavioral disorders (18/24, 75%), neurological signs (13/24, 54%), and dysmorphisms (6/24, 25%) are common. A genotype–phenotype correlation emerged, as DEE is more represented in patients with missense variants located in the ligand-binding domain than in those with truncating or missense variants in other domains (90% vs. 19%, p <.001). Significance: This study suggests that pathogenic YWHAG variants cause a wide range of clinical presentations with variable severity, ranging from mild developmental delay to DEE. In this allelic series, a genotype–phenotype correlation begins to emerge, potentially providing prognostic information for clinical management and genetic counseling.
AB - Objective: YWHAG variant alleles have been associated with a rare disease trait whose clinical synopsis includes an early onset epileptic encephalopathy with predominantly myoclonic seizures, developmental delay/intellectual disability, and facial dysmorphisms. Through description of a large cohort, which doubles the number of reported patients, we further delineate the spectrum of YWHAG-related epilepsy. Methods: We included in this study 24 patients, 21 new and three previously described, with pathogenic/likely pathogenic variants in YWHAG. We extended the analysis of clinical, electroencephalographic, brain magnetic resonance imaging, and molecular genetic information to 24 previously published patients. Results: The phenotypic spectrum of YWHAG-related disorders ranges from mild developmental delay to developmental and epileptic encephalopathy (DEE). Epilepsy onset is in the first 2 years of life. Seizure freedom can be achieved in half of the patients (13/24, 54%). Intellectual disability (23/24, 96%), behavioral disorders (18/24, 75%), neurological signs (13/24, 54%), and dysmorphisms (6/24, 25%) are common. A genotype–phenotype correlation emerged, as DEE is more represented in patients with missense variants located in the ligand-binding domain than in those with truncating or missense variants in other domains (90% vs. 19%, p <.001). Significance: This study suggests that pathogenic YWHAG variants cause a wide range of clinical presentations with variable severity, ranging from mild developmental delay to DEE. In this allelic series, a genotype–phenotype correlation begins to emerge, potentially providing prognostic information for clinical management and genetic counseling.
KW - epilepsy
KW - genotype–phenotype correlation
KW - YWHAG
U2 - 10.1111/epi.17939
DO - 10.1111/epi.17939
M3 - Journal article
C2 - 38491959
AN - SCOPUS:85188435645
VL - 65
SP - 1439
EP - 1450
JO - Epilepsia
JF - Epilepsia
SN - 0013-9580
IS - 5
ER -
ID: 388326362