De novo mutations of STXBP1 in Chinese children with early onset epileptic encephalopathy.

To detect syntaxin-binding protein 1 (STXBP1) mutations in Chinese patients with early onset epileptic encephalopathy (EOEE) of unknown etiology. Targeted next-generation sequencing was used to identify STXBP1 mutations in 143 Chinese patients with EOEE of unknown etiology. A filtering process was applied to prioritize rare variants of potential functional significance. Then Sanger sequencing was employed to validate the parental origin of the variants. Detailed clinical and genetic data were collected for 9 STXBP1-positive patients. Eight de novo heterozygous STXBP1 mutations were identified in 9 patients; 5 were novel mutations (c.1155delC, c.1030-1G>A, c.217G>C, c.268G>C, c.1480_1481 insT) and 3 were previously reported (c.1216C> T, c.1217G>A [2 cases], c.875G>A). Two patients had Ohtahara syndrome and 1 had West syndrome at onset, whereas the other 6 presented with EOEE that did not fit a specific recognized epilepsy syndrome. Six of these patients later evolved to West syndrome. All but 2 cases were prescribed more than 2 antiepileptic drugs (AEDs) plus other regimens. Four subjects showed good responses to levetiracetam (LEV) alone or in combination with other AEDs, and one case (1/3) achieved complete freedom from seizures with a ketogenic diet (KD). All patients exhibited severe to profound global developmental delay. Five novel heterozygous de novo STXBP1 mutations were discovered in patients with EOEE from China. STXBP1 mutational analysis should be performed in cases of EOEE of unknown etiology. LEV as monotherapy or adjunctive therapy with other regimens, as well as KD should be considered for management of this patient group.

Li T ，Cheng M ，Wang J ，Hong S ，Li M ，Liao S ，Xie L ，Jiang L ... -  《-》

[Clinical and genetic characteristics of children with STXBP1 encephalopathy].

Cao JJ ，Ji XN ，Mao YY ，Zhang PP ，Liu WT ，Zhang HZ ，Ding N ，Chen Q ... -  《-》

Loss-of-function mutations of STXBP1 in patients with epileptic encephalopathy.

Epileptic encephalopathy, which commences during early infancy, is a severe epileptic syndrome that manifests as age-dependent seizures and severe developmental delay. The syntaxin-binding protein 1 gene (STXBP1) is one of the genes responsible for epileptic encephalopathy. We conducted a cohort study to analyze STXBP1 in 42 patients with epileptic encephalopathy. We identified four novel mutations: two splicing mutations, a frameshift mutation, and a nonsense mutation. All of these mutations were predicted to cause loss-of-function. This result suggests loss-of-function is a common mechanism underlying STXBP1-related epileptic encephalopathy. The four patients showed epileptic features consistent with STXBP1-related epileptic encephalopathy, but showed variable radiological findings, including brain volume loss and myelination delay.

Yamamoto T ，Shimojima K ，Yano T ，Ueda Y ，Takayama R ，Ikeda H ，Imai K ... -  《-》

Epileptic patients with de novo STXBP1 mutations: Key clinical features based on 24 cases.

Mutations in the syntaxin binding protein 1 gene (STXBP1) have been associated mostly with early onset epileptic encephalopathies (EOEEs) and Ohtahara syndrome, with a mutation detection rate of approximately 10%, depending on the criteria of selection of patients. The aim of this study was to retrospectively describe clinical and electroencephalography (EEG) features associated with STXBP1-related epilepsies to orient molecular screening. We screened STXBP1 in a cohort of 284 patients with epilepsy associated with a developmental delay/intellectual disability and brain magnetic resonance imaging (MRI) without any obvious structural abnormality. We reported on patients with a mutation and a microdeletion involving STXBP1 found using array comparative genomic hybridization (CGH). We found a mutation of STXBP1 in 22 patients and included 2 additional patients with a deletion including STXBP1. In 22 of them, epilepsy onset was before 3 months of age. EEG at onset was abnormal in all patients, suppression-burst and multifocal abnormalities being the most common patterns. The rate of patients carrying a mutation ranged from 25% in Ohtahara syndrome to <5% in patients with an epilepsy beginning after 3 months of age. Epilepsy improved over time for most patients, with an evolution to West syndrome in half. Patients had moderate to severe developmental delay with normal head growth. Cerebellar syndrome with ataxic gait and/or tremor was present in 60%. Our data confirm that STXBP1 mutations are associated with neonatal-infantile epileptic encephalopathies. The initial key features highlighted in the cohort of early epileptic patients are motor seizures either focal or generalized, abnormal initial interictal EEG, and normal head growth. In addition, we constantly found an ongoing moderate to severe developmental delay with normal head growth. Patients often had ongoing ataxic gait with trembling gestures. Altogether these features should help the clinician to consider STXBP1 molecular screening.

Di Meglio C ，Lesca G ，Villeneuve N ，Lacoste C ，Abidi A ，Cacciagli P ，Altuzarra C ，Roubertie A ，Afenjar A ，Renaldo-Robin F ，Isidor B ，Gautier A ，Husson M ，Cances C ，Metreau J ，Laroche C ，Chouchane M ，Ville D ，Marignier S ，Rougeot C ，Lebrun M ，de Saint Martin A ，Perez A ，Riquet A ，Badens C ，Missirian C ，Philip N ，Chabrol B ，Villard L ，Milh M ... -  《-》

A novel mutation in STXBP1 gene in a child with epileptic encephalopathy and an atypical electroclinical pattern.

Romaniello R ，Zucca C ，Tenderini E ，Arrigoni F ，Ragona F ，Zorzi G ，Bassi MT ，Borgatti R ... -  《-》