STXBP1 encephalopathy is associated with awake bruxism

Rezazadeh, Arezoo; Uddin, Mohammed; Snead, O. Carter; Lira, Victor; Silberberg, Alexandra; Weiss, Shelly K.; Donner, Elizabeth; Zak, Maria; Bradbury, Laura; Scherer, Stephen W.; Fasano, Alfonso; Andrade, Danielle M.

doi:10.1016/j.yebeh.2018.12.018

Cited by 19 publications

(17 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Notably, our survival analyses suggested that two down-regulated genes (STXBP1 and PMEPA1) were responsible for both LUAD and LUSC. Syntaxin binding protein 1 (STXBP1) encodes a syntaxin-binding protein, which plays a role in release of neurotransmitters via regulation of syntaxin (a transmembrane attachment protein receptor) (Rezazadeh et al, 2019). A recent article reported the relationship between STXBP1 and prognosis of LUAD (Wang et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

A comparison of mRNA and circRNA expression between squamous cell carcinoma and adenocarcinoma of the lungs

Tian

et al. 2020

Genet. Mol. Biol.

View full text Add to dashboard Cite

Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the two major subtypes of non-small-cell lung cancer (NSCLC). This study aimed to compare mRNA and circRNA expression patterns between LUSC and LUAD. Cancer tissues from 8 LUSC patients and 12 LUAD patients were collected to obtain mRNA and circRNA expression profiles. The differentially expressed mRNAs (DEmRNAs) and circRNAs (DE-circRNAs) between LUSC and LUAD were screened. Afterwards, miRNA-DEcircRNA pairs and miRNA-DEmRNA pairs were predicted to construct a competing endogenous RNAs (ceRNAs) network, followed by functional enrichment analysis and survival analysis. In total, 635 DEmRNAs and 245 DEcircRNAs were obtained. The ceRNA analysis revealed that genes, such as EPHA2, EPHA7, NTRK2, CDK6, hsa_circ_027570, hsa_circ_006089, and hsa-circ_035997, had distinct expression patterns between LUSC and LUAD. Also, functional enrichment analysis indicated that DEmRNAs were mainly enriched in ERK1 and ERK2 cascade. Survival analyses suggested that STXBP1 and PMEPA1 were associated the prognosis of with both LUAD and LUSC, whereas EPHA2 and CDK6 might serve as prognostic factors for LUSC and LUAD, respectively. In conclusion, genes such as EPHA2, EPHA7, NTRK2, and CDK6 had different patterns in the two major histological subtypes of NSCLC. Notably, EPHA2 and CDK6 might be considered as potential therapeutic targets for LUSC and LUAD, respectively.

show abstract

Section: Discussionmentioning

confidence: 99%

A comparison of mRNA and circRNA expression between squamous cell carcinoma and adenocarcinoma of the lungs

Tian

et al. 2020

Genet. Mol. Biol.

View full text Add to dashboard Cite

show abstract

“…Drug resistance, common in RTT Hanefeld variant patients [58] was present only in one out of our six cases. Moderate to severe ID is evident in all six patients, bruxism during wakefulness is present in three out of six girls, a characteristic shared with RTT and STXBP1 -DEE patients [59]. The small number of reported cases with STXBP1 mutations and RTT/RTT-like diagnosis does not allow the definition of a correlation between mutation type and severity of the phenotype or epileptic profile.…”

Section: Discussionmentioning

confidence: 99%

Pathogenic Variants in STXBP1 and in Genes for GABAa Receptor Subunities Cause Atypical Rett/Rett-like Phenotypes

Cogliati

Giorgini

Masciadri

et al. 2019

IJMS

View full text Add to dashboard Cite

Rett syndrome (RTT) is a neurodevelopmental disorder, affecting 1 in 10,000 girls. Intellectual disability, loss of speech and hand skills with stereotypies, seizures and ataxia are recurrent features. Stringent diagnostic criteria distinguish classical Rett, caused by a MECP2 pathogenic variant in 95% of cases, from atypical girls, 40–73% carrying MECP2 variants, and rarely CDKL5 and FOXG1 alterations. A large fraction of atypical and RTT-like patients remain without genetic cause. Next Generation Sequencing (NGS) targeted to multigene panels/Whole Exome Sequencing (WES) in 137 girls suspected for RTT led to the identification of a de novo variant in STXBP1 gene in four atypical RTT and two RTT-like girls. De novo pathogenic variants—one in GABRB2 and, for first time, one in GABRG2—were disclosed in classic and atypical RTT patients. Interestingly, the GABRG2 variant occurred at low rate percentage in blood and buccal swabs, reinforcing the relevance of mosaicism in neurological disorders. We confirm the role of STXBP1 in atypical RTT/RTT-like patients if early psychomotor delay and epilepsy before 2 years of age are observed, indicating its inclusion in the RTT diagnostic panel. Lastly, we report pathogenic variants in Gamma-aminobutyric acid-A (GABAa) receptors as a cause of atypical/classic RTT phenotype, in accordance with the deregulation of GABAergic pathway observed in MECP2 defective in vitro and in vivo models.

show abstract

“…is analysis was able to identify 11 variants (S42P, H103D R190W, R235G, D238E, L256P, P335S, C354Y, L365V, R406C, and G544D) as the most deleterious nsSNPs of the STXBP1 gene by at least 9 computational tools. e di erence between the results of the prediction so ware used in this study revealed the importance of using more than mutations in the Early Infantile Epileptic Encephalopathy patients [9,19,20].…”

Section: Discussionmentioning

confidence: 91%

“…In addition, to determine the role of STXBP1 in Early Infantile Epileptic Encephalopathy, Saitsu et al have identified four heterozygous missense mutations: V48D (Exon 5), C180Y (Exon 7), M443R (Exon 15), and G544D (Exon18) inducing the disease in the cases of one woman and three men [9]. Recently, missenses mutations have been identified in several studies, including the R292H, M262T, and C354Y in three patients with encephalopathy associated with awake bruxism [19]. Furthermore, the M252T mutation has been identified in a man with clonic seizures and epileptic spasms [20], while the R551C mutation has been reported in Stamberger's systematic review [21].…”

Section: Introductionmentioning

confidence: 99%

Molecular Modelling and Dynamics Study of nsSNP in STXBP1 Gene in Early Infantile Epileptic Encephalopathy Disease

Mehdi

Benhnini

Elkarhat

et al. 2019

BioMed Research International

View full text Add to dashboard Cite

Early Infantile Epileptic Encephalopathy (known as Ohtahara Syndrome) is one of the most severe and earliest forms of epilepsy, characterized by early seizures onset. It affects newborns and children between two and six years old. Among the genes that have been associated with early infantile epileptic encephalopathy, the STXBP1 gene, which encodes the Syntaxin binding protein1a that is involved in SNARE complex formation, contributes to synaptic vesicles exocytosis. The aim of this study was to identify the most pathogenic polymorphisms of STXBP1 gene and determine their impact on the structure and stability of Stxbp1 protein. The high-risk nonsynonymous single nucleotide polymorphisms (nsSNPs) in the STXBP1 gene were predicted using 13 bioinformatics tools. The conservation analysis was realized by CONSURF web server. The analysis of the impact of the pathogenic SNPs on the structure of Stxbp1 protein was realized using YASARA software, and the molecular dynamics simulation was performed using GROMACS software. Out of 245 nsSNPs, we identified 11 (S42P, H103D R190W, R235G, D238E, L256P, P335S, C354Y, L365V, R406C, and G544D) as deleterious using in silico prediction tools. Conservation analysis results revealed that all these nsSNPs were located in conserved regions. The comparison of the hydrogen and hydrophobic interactions in the wild type Stxbp1 structure and its mutant forms showed that all these nsSNPs affect the protein structure on different levels. The molecular dynamics simulations revealed that the total of nsSNPs affect the protein stability, residual fluctuation, and the compaction at different levels. This study provides helpful information on high risk nsSNPs that may affect the Stxbp1 protein structure and function. Thus, these variants should be taken into consideration during the genetic screening of patients suffering from early infantile epileptic encephalopathy.

show abstract

STXBP1 encephalopathy is associated with awake bruxism

Cited by 19 publications

References 16 publications

A comparison of mRNA and circRNA expression between squamous cell carcinoma and adenocarcinoma of the lungs

A comparison of mRNA and circRNA expression between squamous cell carcinoma and adenocarcinoma of the lungs

Pathogenic Variants in STXBP1 and in Genes for GABAa Receptor Subunities Cause Atypical Rett/Rett-like Phenotypes

Molecular Modelling and Dynamics Study of nsSNP in STXBP1 Gene in Early Infantile Epileptic Encephalopathy Disease

Contact Info

Product

Resources

About