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Chromosome loci vary by juvenile myoclonic epilepsy subsyndromes: linkage and haplotype analysis applied to epilepsy and EEG 3.5-6.0 Hz polyspike waves.

ABSTRACT: Juvenile myoclonic epilepsy (JME), the most common genetic epilepsy, remains enigmatic because it is considered one disease instead of several diseases. We ascertained three large multigenerational/multiplex JME pedigrees from Honduras with differing JME subsyndromes, including Childhood Absence Epilepsy evolving to JME (CAE/JME; pedigree 1), JME with adolescent onset pyknoleptic absence (JME/pA; pedigree 2), and classic JME (cJME; pedigree 3). All phenotypes were validated, including symptomatic persons with various epilepsies, asymptomatic persons with EEG 3.5-6.0 Hz polyspike waves, and asymptomatic persons with normal EEGs. Two-point parametric linkage analyses were performed with 5185 single-nucleotide polymorphisms on individual pedigrees and pooled pedigrees using four diagnostic models based on epilepsy/EEG diagnoses. Haplotype analyses of the entire genome were also performed for each individual. In pedigree 1, haplotyping identified a 34 cM region in 2q21.2-q31.1 cosegregating with all affected members, an area close to 2q14.3 identified by linkage (Z max = 1.77; pedigree 1). In pedigree 2, linkage and haplotyping identified a 44 cM cosegregating region in 13q13.3-q31.2 (Z max = 3.50 at 13q31.1; pooled pedigrees). In pedigree 3, haplotyping identified a 6 cM cosegregating region in 17q12. Possible cosegregation was also identified in 13q14.2 and 1q32 in pedigree 3, although this could not be definitively confirmed due to the presence of uninformative markers in key individuals. Differing chromosome regions identified in specific JME subsyndromes may contain separate JME disease-causing genes, favoring the concept of JME as several distinct diseases. Whole-exome sequencing will likely identify a CAE/JME gene in 2q21.2-2q31.1, a JME/pA gene in 13q13.3-q31.2, and a cJME gene in 17q12.

SUBMITTER: Wight JE

PROVIDER: S-EPMC4799870 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Chromosome loci vary by juvenile myoclonic epilepsy subsyndromes: linkage and haplotype analysis applied to epilepsy and EEG 3.5-6.0 Hz polyspike waves.

Wight Jenny E JE Nguyen Viet-Huong VH Medina Marco T MT Patterson Christopher C Durón Reyna M RM Molina Yolly Y Lin Yu-Chen YC Martínez-Juárez Iris E IE Ochoa Adriana A Jara-Prado Aurelio A Tanaka Miyabi M Bai Dongsheng D Aftab Sumaya S Bailey Julia N JN Delgado-Escueta Antonio V AV

Molecular genetics & genomic medicine 20160123 2

Juvenile myoclonic epilepsy (JME), the most common genetic epilepsy, remains enigmatic because it is considered one disease instead of several diseases. We ascertained three large multigenerational/multiplex JME pedigrees from Honduras with differing JME subsyndromes, including Childhood Absence Epilepsy evolving to JME (CAE/JME; pedigree 1), JME with adolescent onset pyknoleptic absence (JME/pA; pedigree 2), and classic JME (cJME; pedigree 3). All phenotypes were validated, including symptomati ...[more]

PMID: 27066514

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Project description:Epilepsy is marked by hypersynchronous bursts of neuronal activity, and seizures can propagate variably to any and all areas, leading to brain network dynamic organization. However, the relationship between the network characteristics of scalp EEG and blood oxygenation level-dependent (BOLD) responses in epilepsy patients is still not well known. In this study, simultaneous EEG and fMRI data were acquired in 18 juvenile myoclonic epilepsy (JME) patients. Then, the adapted directed transfer function (ADTF) values between EEG electrodes were calculated to define the time-varying network. The variation of network information flow within sliding windows was used as a temporal regressor in fMRI analysis to predict the BOLD response. To investigate the EEG-dependent functional coupling among the responding regions, modulatory interactions were analyzed for network variation of scalp EEG and BOLD time courses. The results showed that BOLD activations associated with high network variation were mainly located in the thalamus, cerebellum, precuneus, inferior temporal lobe and sensorimotor-related areas, including the middle cingulate cortex (MCC), supplemental motor area (SMA), and paracentral lobule. BOLD deactivations associated with medium network variation were found in the frontal, parietal, and occipital areas. In addition, modulatory interaction analysis demonstrated predominantly directional negative modulation effects among the thalamus, cerebellum, frontal and sensorimotor-related areas. This study described a novel method to link BOLD response with simultaneous functional network organization of scalp EEG. These findings suggested the validity of predicting epileptic activity using functional connectivity variation between electrodes. The functional coupling among the thalamus, frontal regions, cerebellum and sensorimotor-related regions may be characteristically involved in epilepsy generation and propagation, which provides new insight into the pathophysiological mechanisms and intervene targets for JME.

Dataset Information

Chromosome loci vary by juvenile myoclonic epilepsy subsyndromes: linkage and haplotype analysis applied to epilepsy and EEG 3.5-6.0 Hz polyspike waves.

Publications

Chromosome loci vary by juvenile myoclonic epilepsy subsyndromes: linkage and haplotype analysis applied to epilepsy and EEG 3.5-6.0 Hz polyspike waves.

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