Novel Genes of Early-Onset Epileptic Encephalopathies: From Genotype to Phenotypes

Mastrangelo, Mario

doi:10.1016/j.pediatrneurol.2015.04.001

Cited by 30 publications

(27 citation statements)

References 51 publications

(97 reference statements)

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“…In the past decade, the number of genes implicated in epilepsy has been growing exponentially attributed to the advances of next generation sequencing (NGS) technology. These genetic discoveries have revolutionized the clinical practice to evaluate the molecular bases of epilepsy in epilepsy clinics5678910 and lay a foundation for the future development of precision medicine of epilepsy.…”

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confidence: 99%

Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing

Wang

Rao

et al. 2017

Sci Rep

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Genetic factors play a major role in the etiology of epilepsy disorders. Recent genomics studies using next generation sequencing (NGS) technique have identified a large number of genetic variants including copy number (CNV) and single nucleotide variant (SNV) in a small set of genes from individuals with epilepsy. These discoveries have contributed significantly to evaluate the etiology of epilepsy in clinic and lay the foundation to develop molecular specific treatment. However, the molecular basis for a majority of epilepsy patients remains elusive, and furthermore, most of these studies have been conducted in Caucasian children. Here we conducted a targeted exome-sequencing of 63 trios of Chinese epilepsy families using a custom-designed NGS panel that covers 412 known and candidate genes for epilepsy. We identified pathogenic and likely pathogenic variants in 15 of 63 (23.8%) families in known epilepsy genes including SCN1A, CDKL5, STXBP1, CHD2, SCN3A, SCN9A, TSC2, MBD5, POLG and EFHC1. More importantly, we identified likely pathologic variants in several novel candidate genes such as GABRE, MYH1, and CLCN6. Our results provide the evidence supporting the application of custom-designed NGS panel in clinic and indicate a conserved genetic susceptibility for epilepsy between Chinese and Caucasian children.

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confidence: 99%

Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing

Wang

Rao

et al. 2017

Sci Rep

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“…Cognitive and behavioral decline is paralleled by changes in brain connectivity, diminishing excitatory glutamatergic receptor distribution, and decreased neurogenesis . The number of known monogenic determinants of epileptic encephalopathies has grown rapidly . De novo, including somatic mutations are the most frequently encountered while the number of recessive forms remains limited …”

Section: Introductionmentioning

confidence: 99%

“…4 The number of known monogenic determinants of epileptic encephalopathies has grown rapidly. 5 De novo, including somatic mutations are the most frequently encountered while the number of recessive forms remains limited. [6][7][8][9][10] SCN1B, located on 19q13.11, encodes the voltage-gated sodium channel beta 1 subunit, and is known to have multiple isoforms.…”

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confidence: 99%

Confirming the recessive inheritance of SCN1B mutations in developmental epileptic encephalopathy

et al. 2017

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Dominant SCN1B mutations are known to cause several epilepsy syndromes in humans. Only 2 epilepsy patients to date have been reported to have recessive mutations in SCN1B as the likely cause of their phenotype. Here, we confirm the recessive inheritance of 2 novel SCN1B mutations in 5 children from 3 families with developmental epileptic encephalopathy. The recessive inheritance and early death in these patients is consistent with the Dravet-like phenotype observed in Scn1b mice. The 'negative' clinical exome in one of these families highlights the need to consider recessive mutations in the interpretation of variants in typically dominant genes.

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“…The causes of the EEE are heterogeneous, but most of them are probably genetic, with an MRI not presenting any structural abnormalities that can explain it. Currently, several dozen of genes were involved in the EEE [2]. Here we will describe the phenotype associated to the most frequently mutated genes found in the EEE, and we will question the usefulness of finding a mutation in the therapeutic strategy.…”

Section: Introductionmentioning

confidence: 99%

Severe neonatal seizures: From molecular diagnosis to precision therapy?

et al. 2016

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Novel Genes of Early-Onset Epileptic Encephalopathies: From Genotype to Phenotypes

Cited by 30 publications

References 51 publications

Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing

Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing

Confirming the recessive inheritance of SCN1B mutations in developmental epileptic encephalopathy

Severe neonatal seizures: From molecular diagnosis to precision therapy?

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