STXBP6 Gene Mutation: A New Form of SNAREopathy Leads to Developmental Epileptic Encephalopathy

Vinci, Mirella; Costanza, Carola; Galati Rando, Rosanna; Treccarichi, Simone; Saccone, Salvatore; Carotenuto, Marco; Roccella, Michele; Calì, Francesco; Elia, Maurizio; Vetri, Luigi

doi:10.3390/ijms242216436

Cited by 8 publications

(4 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All of the genes constitutive of the SNARE complex (VAMP2synaptobrevin; STX1A-synaptobrevin1; SPAP25 gene), except amysin, have already been described as being responsible for epilepsy, DEE, and/or neurodevelopmental disorders when mutated [31,32]. Ours is the first study to show evidence that a mutation in the STXBP6 gene correlates with a form of DEE as a comorbidity with autism spectrum disorder [17]. The causative mutation detected by exome sequencing determined the phenotypic picture by altering the synaptic vesicle fusion process essential to their exocytosis.…”

Section: Discussionmentioning

confidence: 77%

“…STXBP6 (syntaxin-binding protein 6-OMIM #607958) is a gene coding for the protein amisyn, which is capable of binding components of the SNARE complex by regulating the fusion of synaptic vesicles with the cell membrane and thus playing a role in neurotransmitter homeostasis. Our exome sequencing showed a de novo c.313_323delGAAAATGCTTT variant in the STXBP6 gene (NM_014178.8) [17]. This de novo deletion resulted in a premature stop codon at p.Glu105Ter resulting in a truncated protein (105 versus 210 amino acids).…”

Section: New Candidate Genesmentioning

confidence: 86%

“…Next-generation sequencing (NGS) visualization with the IGV of the deletions of GAAAATGCTTT nucleotides (reverse) in the STXBP6 gene. Reads total: 123 (AAAGCATTTTC = 48 reads; deletion = 54 reads) (modified from [17]). (c) Biosynthetic pathway of the allopregnanolone from progesterone.…”

Section: New Candidate Genesmentioning

confidence: 99%

See 2 more Smart Citations

Whole Exome Sequencing as a First-Line Molecular Genetic Test in Developmental and Epileptic Encephalopathies

Vetri,

Calì,

Saccone

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

Developmental and epileptic encephalopathies (DEE) are severe neurodevelopmental disorders characterized by recurrent, usually early-onset, epileptic seizures accompanied by developmental impairment often related to both underlying genetic etiology and abnormal epileptiform activity. Today, next-generation sequencing technologies (NGS) allow us to sequence large portions of DNA quickly and with low costs. The aim of this study is to evaluate the use of whole-exome sequencing (WES) as a first-line molecular genetic test in a sample of subjects with DEEs characterized by early-onset drug-resistant epilepsies, associated with global developmental delay and/or intellectual disability (ID). We performed 82 WESs, identifying 35 pathogenic variants with a detection rate of 43%. The identified variants were highlighted on 29 different genes including, 3 new candidate genes (KCNC2, STXBP6, DHRS9) for DEEs never identified before. In total, 23 out of 35 (66%) de novo variants were identified. The most frequently identified type of inheritance was autosomal dominant de novo (60%) followed by autosomal recessive in homozygosity (17%) and heterozygosity (11%), autosomal dominant inherited from parental mosaicism (6%) and X-linked dominant de novo (6%). The most frequent mutations identified were missense (75%) followed by frameshift deletions (16%), frameshift duplications (5%), and splicing mutations (3%). Considering the results obtained in the present study we support the use of WES as a form of first-line molecular genetic testing in DEEs.

show abstract

Section: Discussionmentioning

confidence: 77%

Section: New Candidate Genesmentioning

confidence: 86%

See 1 more Smart Citation

Whole Exome Sequencing as a First-Line Molecular Genetic Test in Developmental and Epileptic Encephalopathies

Vetri,

Calì,

Saccone

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…A block of variants in STXBP6 were associated with CVB_total. Syntaxin-binding protein 6 (STXBP6) is an essential component of the SNAP receptor (SNARE) complex and plays an important role in synaptic transmission and neuronal vesicle trafficking; mutations of genes encoding the SNARE proteins are associated with various neurological disorders 30 , 31 . Common variants in STXBP6 were reported to be linked to cortical surface area 32 and rate of cognitive decline in Alzheimer’s disease 33 .…”

Section: Discussionmentioning

confidence: 99%

A genome-wide association study of Chinese and English language phenotypes in Hong Kong Chinese children

Lin,

Shi,

Zhang

et al. 2024

npj Sci. Learn.

View full text Add to dashboard Cite

Dyslexia and developmental language disorders are important learning difficulties. However, their genetic basis remains poorly understood, and most genetic studies were performed on Europeans. There is a lack of genome-wide association studies (GWAS) on literacy phenotypes of Chinese as a native language and English as a second language (ESL) in a Chinese population. In this study, we conducted GWAS on 34 reading/language-related phenotypes in Hong Kong Chinese bilingual children (including both twins and singletons; total N = 1046). We performed association tests at the single-variant, gene, and pathway levels. In addition, we tested genetic overlap of these phenotypes with other neuropsychiatric disorders, as well as cognitive performance (CP) and educational attainment (EA) using polygenic risk score (PRS) analysis. Totally 5 independent loci (LD-clumped at r2 = 0.01; MAF > 0.05) reached genome-wide significance (p < 5e-08; filtered by imputation quality metric Rsq>0.3 and having at least 2 correlated SNPs (r2 > 0.5) with p < 1e-3). The loci were associated with a range of language/literacy traits such as Chinese vocabulary, character and word reading, and rapid digit naming, as well as English lexical decision. Several SNPs from these loci mapped to genes that were reported to be associated with EA and other neuropsychiatric phenotypes, such as MANEA and PLXNC1. In PRS analysis, EA and CP showed the most consistent and significant polygenic overlap with a variety of language traits, especially English literacy skills. To summarize, this study revealed the genetic basis of Chinese and English abilities in a group of Chinese bilingual children. Further studies are warranted to replicate the findings.

show abstract

PPP2R5E: New gene potentially involved in specific learning disorders and myopathy

Musumeci,

Vinci,

Verbinnen

et al. 2025

Gene

View full text Add to dashboard Cite

STXBP6 Gene Mutation: A New Form of SNAREopathy Leads to Developmental Epileptic Encephalopathy

Cited by 8 publications

References 56 publications

Whole Exome Sequencing as a First-Line Molecular Genetic Test in Developmental and Epileptic Encephalopathies

Whole Exome Sequencing as a First-Line Molecular Genetic Test in Developmental and Epileptic Encephalopathies

A genome-wide association study of Chinese and English language phenotypes in Hong Kong Chinese children

PPP2R5E: New gene potentially involved in specific learning disorders and myopathy

Contact Info

Product

Resources

About