Multiscale Functional Clustering Reveals Frequency Dependent Brain Organization in Type II Focal Cortical Dysplasia With Sleep Hypermotor Epilepsy

2019 ◽  
Vol 66 (10) ◽  
pp. 2831-2839
Author(s):  
Stefania Coelli ◽  
Eleonora Maggioni ◽  
Annalisa Rubino ◽  
Chiara Campana ◽  
Lino Nobili ◽  
...  
Keyword(s):  
Focal Cortical Dysplasia ◽  
Cortical Dysplasia ◽  
Type Ii ◽  
Brain Organization ◽  
Frequency Dependent ◽  
Functional Clustering

scholarly journals Transcriptomic profiling of high- and low-spiking regions reveals novel epileptogenic mechanisms in focal cortical dysplasia type II patients

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Arpna Srivastava ◽  
Krishan Kumar ◽  
Jyotirmoy Banerjee ◽  
Manjari Tripathi ◽  
Vivek Dubey ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Focal Cortical Dysplasia ◽  
Phospholipid Metabolism ◽  
Cortical Dysplasia ◽  
Type Ii ◽  
Tissue Samples ◽  
Significant Enrichment ◽  
Gene Expression Studies ◽  
Oligodendrocyte Development ◽  
High Throughput Gene Expression

AbstractFocal cortical dysplasia (FCD) is a malformation of the cerebral cortex with poorly-defined epileptogenic zones (EZs), and poor surgical outcome in FCD is associated with inaccurate localization of the EZ. Hence, identifying novel epileptogenic markers to aid in the localization of EZ in patients with FCD is very much needed. High-throughput gene expression studies of FCD samples have the potential to uncover molecular changes underlying the epileptogenic process and identify novel markers for delineating the EZ. For this purpose, we, for the first time performed RNA sequencing of surgically resected paired tissue samples obtained from electrocorticographically graded high (MAX) and low spiking (MIN) regions of FCD type II patients and autopsy controls. We identified significant changes in the MAX samples of the FCD type II patients when compared to non-epileptic controls, but not in the case of MIN samples. We found significant enrichment for myelination, oligodendrocyte development and differentiation, neuronal and axon ensheathment, phospholipid metabolism, cell adhesion and cytoskeleton, semaphorins, and ion channels in the MAX region. Through the integration of both MAX vs non-epileptic control and MAX vs MIN RNA sequencing (RNA Seq) data, PLP1, PLLP, UGT8, KLK6, SOX10, MOG, MAG, MOBP, ANLN, ERMN, SPP1, CLDN11, TNC, GPR37, SLC12A2, ABCA2, ABCA8, ASPA, P2RX7, CERS2, MAP4K4, TF, CTGF, Semaphorins, Opalin, FGFs, CALB2, and TNC were identified as potential key regulators of multiple pathways related to FCD type II pathology. We have identified novel epileptogenic marker elements that may contribute to epileptogenicity in patients with FCD and could be possible markers for the localization of EZ.

scholarly journals Genome-wide DNA Methylation and RNAseq Analyses Identify Aberrant Signalling Pathways in Focal Cortical Dysplasia (FCD) Type II

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Aparna Banerjee Dixit ◽  
Devina Sharma ◽  
Manjari Tripathi ◽  
Arpna Srivastava ◽  
Debasmita Paul ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Focal Cortical Dysplasia ◽  
Cortical Dysplasia ◽  
Signalling Pathways ◽  
Type Ii ◽  
Genome Wide

Scalp High Frequency Oscillations Associated with Rhythmic Spikes Activity in Focal Cortical Dysplasia Type II

2016 ◽  
Vol 33 (3) ◽  
pp. 672-682
Author(s):  
Azusa Tabata ◽  
Keiko Hara ◽  
Motoki Inaji ◽  
Natsumi Tamada ◽  
Reina Kawanami ◽  
...  
Keyword(s):  
High Frequency ◽  
Focal Cortical Dysplasia ◽  
Cortical Dysplasia ◽  
Type Ii ◽  
High Frequency Oscillations

scholarly journals Superior Frontal Sulcus Focal Cortical Dysplasia Type II: An MRI, PET, and Quantified SEEG Study

2019 ◽  
Vol 10 ◽  
Author(s):  
Chao Zhang ◽  
Bao-tian Zhao ◽  
Aileen McGonigal ◽  
Wen-han Hu ◽  
Xiu Wang ◽  
...  
Keyword(s):  
Focal Cortical Dysplasia ◽  
Cortical Dysplasia ◽  
Type Ii ◽  
Superior Frontal Sulcus

Somatic variants in new candidate genes identified in focal cortical dysplasia type II

Epilepsia ◽  
2020 ◽  
Vol 61 (4) ◽  
pp. 667-678
Author(s):  
Zhongbin Zhang ◽  
Kai Gao ◽  
Qingzhu Liu ◽  
Jiapeng Zhou ◽  
Xiyuan Li ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Focal Cortical Dysplasia ◽  
Cortical Dysplasia ◽  
Type Ii

scholarly journals Type II focal cortical dysplasia: Electroclinical phenotype and surgical outcome related to imaging

Epilepsia ◽  
2012 ◽  
Vol 53 (2) ◽  
pp. 349-358 ◽  
Author(s):  
Francine Chassoux ◽  
Elisabeth Landré ◽  
Charles Mellerio ◽  
Baris Turak ◽  
Michael W. Mann ◽  
...  
Keyword(s):  
Surgical Outcome ◽  
Focal Cortical Dysplasia ◽  
Cortical Dysplasia ◽  
Type Ii

Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy

2015 ◽  
Vol 21 (4) ◽  
pp. 395-400 ◽  
Author(s):  
Jae Seok Lim ◽  
Woo-il Kim ◽  
Hoon-Chul Kang ◽  
Se Hoon Kim ◽  
Ah Hyung Park ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Focal Cortical Dysplasia ◽  
Intractable Epilepsy ◽  
Cortical Dysplasia ◽  
Type Ii

scholarly journals Somatic mutation involving diverse genes leads to a spectrum of focal cortical malformations

2021 ◽  
Author(s):  
Dulcie Lai ◽  
Meethila Gade ◽  
Edward Yang ◽  
Hyun Yong Koh ◽  
Nicole M. Walley ◽  
...  
Keyword(s):  
Focal Cortical Dysplasia ◽  
Hippocampal Sclerosis ◽  
Cortical Development ◽  
Copy Number Variants ◽  
Cortical Dysplasia ◽  
Disease Genes ◽  
Type I ◽  
Type Ii ◽  
Loss Of Function ◽  
Brain Malformations

Post-zygotically acquired genetic variants, or somatic variants, that arise during cortical development have emerged as important causes of focal epilepsies, particularly those due to malformations of cortical development. Pathogenic somatic variants have been identified in many genes within the PI3K-AKT3-mTOR-signaling pathway in individuals with hemimegalencephaly and focal cortical dysplasia (type II), and more recently in SLC35A2 in individuals with focal cortical dysplasia (type I) or non-dysplastic epileptic cortex. Given the expanding role of somatic variants across different brain malformations, we sought to delineate the landscape of somatic variants in a large cohort of patients who underwent epilepsy surgery with hemimegalencephaly or focal cortical dysplasia. We evaluated samples from 123 children with hemimegalencephaly (n=16), focal cortical dysplasia type I and related phenotypes (n=48), focal cortical dysplasia type II (n=44), or focal cortical dysplasia type III (n=15) classified using imaging and pathological findings. We performed high-depth exome sequencing in brain tissue-derived DNA from each case and identified somatic single nucleotide, indel, and large copy number variants. In 75% of individuals with hemimegalencephaly and 29% with focal cortical dysplasia type II, we identified pathogenic variants in PI3K-AKT-mTOR pathway genes. Four of 48 cases with focal cortical dysplasia type I (8%) had a likely pathogenic variant in SLC35A2. While no other gene had multiple disease-causing somatic variants across the focal cortical dysplasia type I cohort, four individuals in this group had a single pathogenic or likely pathogenic somatic variant in CASK, KRAS, NF1, and NIPBL, genes associated with neurodevelopmental disorders. No rare pathogenic or likely pathogenic somatic variants in any neurological disease genes like those identified in the focal cortical dysplasia type I cohort were found in 63 neurologically normal controls (P = 0.017), suggesting a role for these novel variants. We also identified a somatic loss-of-function variant in the known epilepsy gene, PCDH19, present in a very small number of alleles in the dysplastic tissue from a female patient with focal cortical dysplasia IIIa with hippocampal sclerosis. In contrast to focal cortical dysplasia type II, neither focal cortical dysplasia type I nor III had somatic variants in genes that converge on a unifying biological pathway, suggesting greater genetic heterogeneity compared to type II. Importantly, we demonstrate that FCD types I, II, and III, are associated with somatic gene variants across a broad range of genes, many associated with epilepsy in clinical syndromes caused by germline variants, as well as including some not previously associated with radiographically evident cortical brain malformations.

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