Customized targeted massively parallel sequencing enables the identification of novel pathogenic variants in Tunisian patients with Developmental and Epileptic Encephalopathy
Copyright policy )Customized targeted massively parallel sequencing enables the identification of novel pathogenic variants in Tunisian patients with Developmental and Epileptic Encephalopathy
AbstractBackgroundDevelopmental and Epileptic Encephalopathies stand for a heterogenous group of epileptic syndromes, where the epileptic activity itself and/or the etiology contribute to cognitive and behavioral impairment. In recent decades, genetic etiology has increasingly been recognized as the cause of Developmental and Epileptic Encephalopathies and numerous genes have been identified, thanks to advances in genetic technologies. These discoveries have enabled precision treatments for several syndromes. Therefore, the identification of the causal variant in a gene is an intrinsic starting point to specify a precision therapy for the patient and an adequate management.ResultsWe developed a custom panel for Next Generation Sequencing of the coding sequences of 116 genes in individuals with Developmental and Epileptic Encephalopathy from the Tunisian population. Segregation analyses as well as in silico studies have been conducted to assess the identified variants’ pathogenicity. We report 12 pathogenic variants inSCN1A,CHD2,CDKL5,SZT2,KCNT1,GNAO1,PCDH19,MECP2,GRIN2A,andSYNGAP1in patients with Developmental and Epileptic Encephalopathy. Five of these variants are novel: “c.149delA, p.(Asn50MetfsTer26)” inCDKL5; “c.3616C>T, p.(Arg1206Ter)” inSZT2; “c.111_113del, p.(Leu39del)” inGNAO1; “c.1435G>C , p.(Asp479His)” inPCDH19;as well as “c.2143delC, p. (Arg716GlyfsTer10)”inSYNGAP1. Additionally, for five of our patients, the genetic result facilitated the choice of the appropriate treatment.ConclusionThis is the first report of a custom gene panel to identify genetic variants implicated in Developmental and Epileptic Encephalopathy in the Tunisian population as well as the North African region (Tunisia, Egypt, Libya, Algeria, Morocco) with a diagnostic rate of 30%. This high-throughput sequencing panel has considerably improved the rate of positive diagnosis of Developmental and Epileptic Encephalopathy in the Tunisian population, which was less than 15% using Sanger sequencing. The benefit of genetic testing in these patients was approved by both physicians and parents.
- FACULTE DES SCIENCES DE SFAX Tunisia
- Centre of Biotechnology of Sfax Tunisia
- Hopital Universitaire Hedi Chaker Tunisia
- University of Sfax Tunisia
Male, Adult, Sanger sequencing, Tunisia, Adolescent, diagnosis, Population, Encephalopathy, Gene, Biochemistry, Genetics and Molecular Biology, Exome Sequencing, Genetics, Humans, DNA sequencing, developmental and epileptic encephalopathy, RC346-429, Child, panel, Molecular Biology, Biology, Internal medicine, Epilepsy, High-Throughput Nucleotide Sequencing, Infant, Life Sciences, sequencing, Massive parallel sequencing, Standards and Guidelines for Genetic Variant Interpretation, Nucleotide Metabolism and Enzyme Regulation, Environmental health, variant, Child, Preschool, FOS: Biological sciences, Mutation, Molecular Basis of Rett Syndrome and Related Disorders, Medicine, Original Article, Female, Neurology. Diseases of the nervous system, Spasms, Infantile, Neuroscience
Male, Adult, Sanger sequencing, Tunisia, Adolescent, diagnosis, Population, Encephalopathy, Gene, Biochemistry, Genetics and Molecular Biology, Exome Sequencing, Genetics, Humans, DNA sequencing, developmental and epileptic encephalopathy, RC346-429, Child, panel, Molecular Biology, Biology, Internal medicine, Epilepsy, High-Throughput Nucleotide Sequencing, Infant, Life Sciences, sequencing, Massive parallel sequencing, Standards and Guidelines for Genetic Variant Interpretation, Nucleotide Metabolism and Enzyme Regulation, Environmental health, variant, Child, Preschool, FOS: Biological sciences, Mutation, Molecular Basis of Rett Syndrome and Related Disorders, Medicine, Original Article, Female, Neurology. Diseases of the nervous system, Spasms, Infantile, Neuroscience
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