Clinical whole exome sequencing revealed de novo heterozygous stop-gain and missense variants in the STXBP1 gene associated with epilepsy in Saudi families

Muhammad Imran Naseer; Angham Abdulrhman Abdulkareem; Mahmood Rasool; Bader Shirah; Hussein Algahtani; Osama Y Muthaffar; Peter Natesan Pushparaj

doi:10.1016/j.sjbs.2022.103309

Clinical whole exome sequencing revealed de novo heterozygous stop-gain and missense variants in the STXBP1 gene associated with epilepsy in Saudi families

Saudi J Biol Sci. 2022 Jul;29(7):103309. doi: 10.1016/j.sjbs.2022.103309. Epub 2022 May 20.

Authors

Muhammad Imran Naseer^{1

2}, Angham Abdulrhman Abdulkareem^{1

3}, Mahmood Rasool^{1

2}, Bader Shirah⁴, Hussein Algahtani⁵, Osama Y Muthaffar⁶, Peter Natesan Pushparaj^{1

2}

Affiliations

¹ Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
² Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
³ Faculty of Science, Department of Biochemistry, King Abdulaziz University, Jeddah, Saudi Arabia.
⁴ Department of Neuroscience, King Faisal Specialist Hospital & Research Centre, Jeddah, Saudi Arabia.
⁵ King Abdulaziz Medical City, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia.
⁶ Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

Abstract

Intellectual disability and developmental encephalopathies are mostly linked with infant epilepsy. Epileptic encephalopathy is a term that is used to define association between developmental delay and epilepsy. Mutations in the STXBP1 (Syntaxin-binding protein 1) gene have been previously reported in association with multiple severe early epileptic encephalopathies along with many neurodevelopmental disorders. Among the disorders produced due to any mutations in the STXBP1 gene is developmental and epileptic encephalopathy 4 (OMIM: 612164), is an autosomal dominant neurologic disorder categorized by the onset of tonic seizures in early infancy (usually in the first months of life). In this article, we report two Saudi families one with de novo heterozygous stop-gain mutation c.364C > T and a novel missense c. 305C > A p.Ala102Glu in exon 5 of the STXBP1 gene (OMIM: 602926) lead to development of epileptic encephalopathy 4. The variants identified in the current study broadened the genetic spectrum of STXBP1 gene related with diseases, which will help to add in the literature and benefit to the studies addressing this disease in the future.

Keywords: DNA, Deoxyribonucleic acid; Developmental and Epileptic Encephalopathy 4; EEG, Electroencephalogram; Heterozygous; MRI, Magnetic Resonance Imaging; STXBP1; STXBP1, Syntaxin-binding protein 1; Saudi Arabia; Stop-Gain Mutation; WES, Whole exom sequencing.