Precise detection of low-level somatic mutation in resected epilepsy brain tissue

AbstractLow-level somatic mutations have been shown to be the major genetic etiology of intractable epilepsy. The extents thereof, however, have yet to be systematically and accurately explored in a large cohort of resected epilepsy brain tissues. Moreover, clinically useful and precise analysis tools for detecting low-level somatic mutations from unmatched formalin-fixed paraffin-embedded (FFPE) brain samples, the most clinically relevant samples, are still lacking. In total, 446 tissues samples from 232 intractable epilepsy patients with various brain pathologies were analyzed using deep sequencing (average read depth, 1112x) of known epilepsy-related genes (up to 28 genes) followed by confirmatory site-specific amplicon sequencing. Pathogenic mutations were discovered in 31.9% (74 of 232) of the resected epilepsy brain tissues and were recurrently found in only eight major focal epilepsy genes, includingAKT3, DEPDC5, MTOR, PIK3CA, TSC1, TSC2, SCL35A2, andBRAF. Somatic mutations, two-hit mutations, and germline mutations accounted for 22.0% (51), 0.9% (2), and 9.1% (21) of the patients with intractable epilepsy, respectively. The majority of pathogenic somatic mutations (62.3%, 33 of 53) had a low variant allelic frequency of less than 5%. The use of deep sequencing replicates in the eight major focal epilepsy genes robustly increased PPVs to 50 –100% and sensitivities to 71–100%. In an independent FCDII cohort of only unmatched FFPE brain tissues, deep sequenci...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

Related Links:

Authors: Fernandes MJS, Carletti CO, Sierra de Araújo LF, Santos RC, Reis J Abstract A growing number of studies have shown that exposure to air pollutants such as particulate matter and gases can cause cardiovascular, neurodegenerative and psychiatric diseases. The severity of the changes depends on several factors such as exposure time, age and gender. Inflammation has been considered as one of the main factors associated with the generation of these diseases. Here we present some cellular mechanisms activated by air pollution that may represent risk factors for epilepsy and drug resistance associated to e...
Source: Revue Neurologique - Category: Neurology Tags: Rev Neurol (Paris) Source Type: research
ConclusionThis case highlights the importance of genetics shaping phenotypes and that consideration should always be given to a full relevant family history.  It also shows a rare case of rapidly progressive dementia confirmed due to CJD with a likely underlying familial predisposition.
Source: Age and Ageing - Category: Geriatrics Source Type: research
Journal of Perinatology, Published online: 16 September 2019; doi:10.1038/s41372-019-0494-7Association of perinatal factors of epilepsy in very low birth weight infants, using a nationwide database in Japan
Source: Journal of Perinatology - Category: Perinatology & Neonatology Authors: Source Type: research
Interest in cannabis as a treatment for people living with epilepsy has increased over the last several years. The use of cannabis for epilepsy has been described in anecdotal reports for centuries. [1 –3] Colorado voters passed a medicinal cannabis law allowing use for specific diagnoses in November 2000. Despite many new treatments becoming available in the last 20 years, including new antiseizure medications, neurostimulation, and improvements in surgical techniques and etiologic identificati on, many children living with epilepsy do not have well-controlled seizures.
Source: Seizure: European Journal of Epilepsy - Category: Neurology Authors: Source Type: research
Publication date: Available online 13 September 2019Source: Journal of Clinical NeuroscienceAuthor(s): Jie Bai, Wen-Juan Zhang, Zhi-Fang Ruan, Bei-Bei Chen, Gang Zhao, Dong Wang, Jing-Xia Dang, Yong-Hong LiuAbstractPhotosensitive is probably caused by multiple factors including gender, familiar, etc. We aim to study the clinical and EEG features of Chinese Han patients with photosensitivity. A total of 5482 consecutive patients with possible epilepsy from 3 center in China. Of the 73 patients with PPR to IPS, 48 were female. 69.9% patients were evoked by frequency ranged 8 Hz–25 Hz, with accompanying seizures in ...
Source: Journal of Clinical Neuroscience - Category: Neuroscience Source Type: research
Publication date: November 2019Source: Epilepsy &Behavior, Volume 100, Part AAuthor(s): Florentina M.E. Pinckaers, Mebeline E. Boon, Marian H.J.M. MajoieAbstractPurposeWhile levetiracetam (LEV) usage is a known risk factor for psychosis in epilepsy, the modulating effect of certain patient and treatment characteristics on the risk of psychosis has yet to be fully elucidated.MethodsIn our tertiary epilepsy center, 84 patients with psychotic symptoms during LEV usage and 100 controls without psychotic symptoms during LEV usage were selected. Patient records were reviewed including demographics, medical history, antiepile...
Source: Epilepsy and Behavior - Category: Neurology Source Type: research
Publication date: November 2019Source: Epilepsy &Behavior, Volume 100, Part AAuthor(s): Kai-Chieh Chang, Tzy-Haw Wu, Jean Ching-Yuan Fann, Sam Li- sheng Chen, Amy Ming-Fang Yen, Sherry Yueh-Hsia Chiu, Fei-Chi Liu, Hsiu-Hsi Chen, Horng Huei LiouAbstractBackgroundThe onset of epileptic seizures is influenced by weather, which is multifactorial. It is unknown which specific weather factors affect the occurrence of seizures.ObjectivesWe studied the correlation between the onset of epileptic seizures and multiple weather parameters based on a population-based registry profile.MethodsWe determined the number of patients who ...
Source: Epilepsy and Behavior - Category: Neurology Source Type: research
ConclusionsIn our sample of adult patients with focal DRE, female gender and being diagnosed with a mood disorder were the only factors significantly associated with a poorer HRQoL. While clinical care often focuses on seizure control, epilepsy-related factors such as seizure frequency were not shown to have a significant influence on HRQoL. We suggest that an early comprehensive psychiatric evaluation and intervention can help improve HRQoL in these patients.
Source: Epilepsy and Behavior - Category: Neurology Source Type: research
ConclusionsThese preliminary findings suggest that prenatal AED exposure may alter early processing of emotionally and linguistically relevant sound information.
Source: Epilepsy and Behavior - Category: Neurology Source Type: research
Publication date: Available online 13 September 2019Source: Epilepsy &BehaviorAuthor(s): Omar Abdel-Mannan, Elaine Hughes, Colin DunkleyAbstractEpilepsy-related death in children and young people deserves understanding and intervention along with epilepsy-related deaths in adults. Risk of death from epilepsy varies at different ages, and the specific calculations of risk remains complex and varies between studies. There have been several UK studies examining factors associated with epilepsy-related deaths. A UK national audit with other national initiatives has evidenced improving quality of care and more recently allo...
Source: Epilepsy and Behavior - Category: Neurology Source Type: research
More News: Brain | Epilepsy | Genetics | Neurology