Article
Genetics & Heredity
Alexandra Roston, Dan Evans, Harinder Gill, Margaret McKinnon, Bertrand Isidor, Benjamin Cogne, Jill Mwenifumbo, Clara van Karnebeek, Jianghong An, Steven J. M. Jones, Matthew Farrer, Michelle Demos, Mary Connolly, William T. Gibson
Summary: Rare coding variants in SETD1B can lead to a diagnosable syndrome with shared phenotype of intellectual disability, language delay, conserved musculoskeletal findings, and potentially treatment-refractory seizures. Next-generation sequencing among a cohort of paediatric patients with epilepsy provides supporting evidence for these findings, suggesting that these variants may contribute as a risk factor for epilepsy, autism, and other neurodevelopmental phenotypes. Longitudinal studies are needed to further understand the role of SETD1B in neurodevelopmental disorders and other systemic diseases.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Genetics & Heredity
Stefanie Brock, Tim Vanderhasselt, Sietske Vermaning, Kathelijn Keymolen, Luc Regal, Romina Romaniello, Dagmar Wieczorek, Tim Matthias Storm, Karin Schaeferhoff, Ute Hehr, Alma Kuechler, Ingeborg Kraegeloh-Mann, Tobias B. Haack, Esmee Kasteleijn, Rachel Schot, Grazia Maria Simonetta Mancini, Richard Webster, Shekeeb Mohammad, Richard J. Leventer, Ghayda Mirzaa, William B. Dobyns, Nadia Bahi-Buisson, Marije Meuwissen, Anna C. Jansen, Katrien Stouffs
Summary: This study reviewed clinical and imaging features of 12 patients with pathogenic TUBB2A variants, finding 8 novel and one recurrent variants. Most patients developed seizures in early life, intellectual disability, severe motor developmental delay, and cerebral cortex abnormalities. The imaging phenotype associated with pathogenic TUBB2A variants is highly variable.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Multidisciplinary Sciences
Gloriia Novikova, Manav Kapoor, T. C. W. Julia, Edsel M. Abud, Anastasia G. Efthymiou, Steven X. Chen, Haoxiang Cheng, John F. Fullard, Jaroslav Bendl, Yiyuan Liu, Panos Roussos, Johan Lm Bjorkegren, Yunlong Liu, Wayne W. Poon, Ke Hao, Edoardo Marcora, Alison M. Goate
Summary: This study integrates Alzheimer's disease (AD) GWAS data with myeloid cell genomics, and reports that myeloid active enhancers are most burdened by AD risk alleles. The authors also nominate candidate causal regulatory elements, variants and genes that likely modulate the risk for AD.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Dana Jaber, Cyril Gitiaux, Sophie Blesson, Florent Marguet, David Buard, Maritzaida Varela Salgado, Anna Kaminska, Julien Saada, Catherine Fallet-Bianco, Jelena Martinovic, Annie Laquerriere, Judith Melki
Summary: We report pathogenic heterozygous missense de novo variants in SCN1A in three unrelated individuals with AMC. These variants are newly occurring, demonstrating the critical role of SCN1A in prenatal motor development. Lack of motor denervation in affected individuals suggests that AMC is caused by brain involvement.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Neurosciences
Marco Ledri, My Andersson, Jenny Wickham, Merab Kokaia
Summary: The advent of optogenetic tools has revolutionized our understanding of the brain by offering precise manipulation of neurons with temporal precision. In epilepsy research, these tools have played a crucial role in understanding seizure generation and exploring therapeutic strategies. They have provided insights into the initiation of seizures, interactions between different brain regions, and potential for real-time control of seizure activity.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
Helene Sundelin, Jonas Soderling, Peter Bang, Jenny Bolk
Summary: The study aimed to evaluate the risk of autism in children with pediatric ischemic stroke and their relatives. It found that the risk of autism significantly increased in individuals with ischemic stroke, especially those with comorbid epilepsy. Even in patients without epilepsy and adverse motor outcomes, the risk of autism remained elevated.
Article
Clinical Neurology
Basel Taweel, Anthony G. Marson, Nasir Mirza
Summary: This study aims to predict the efficacy of drugs for monogenic epilepsies, focusing on Dravet syndrome. They have developed a computational method and successfully predicted drugs that are effective for this syndrome.
Article
Clinical Neurology
Michael C. Jin, Jonathon J. Parker, Michael Zhang, Zack A. Medress, Casey H. Halpern, Gordon Li, John K. Ratliff, Gerald A. Grant, Robert S. Fisher, Stephen Skirboll
Summary: The occurrence of early and late PNSE was associated with specific neurosurgical pathologies and increased mortality. These findings provide a foundation for validating clinical and perioperative risk factors prospectively and help identify patients who require heightened diagnostic suspicion for PNSE.
JOURNAL OF NEUROSURGERY
(2021)
Article
Genetics & Heredity
Lynn Rose Tao, Yixuan Ye, Hongyu Zhao
Summary: This study developed a novel breast cancer risk detection application, BRECARDA, which personalized risk assessment using artificial intelligence neural networks and achieved high accuracy and area under the curve in testing. It can assist doctors in breast cancer diagnosis and evaluation.
JOURNAL OF MEDICAL GENETICS
(2023)
Review
Microbiology
Irati Romero-Garmendia, Koldo Garcia-Etxebarria
Summary: The role of microbiota in colorectal cancer is significant and is associated with interactions with the host and host genetics. Studying these interactions can provide insights into the biological pathways and mechanisms of colorectal cancer, leading to feasible measures for prevention and treatment.
Article
Dentistry, Oral Surgery & Medicine
Kathleen S. Paul, Christopher M. Stojanowski, Toby Hughes, Alan Brook, Grant C. Townsend
Summary: The study reveals high levels of genetic correlation in human anterior dental morphology, particularly between corresponding teeth on both sides, and to a lesser extent among permanent dental traits. Results indicate the presence of a morphological module spanning deciduous and permanent dentition, with lower correlation among traits within individual teeth.
ARCHIVES OF ORAL BIOLOGY
(2021)
Article
Clinical Neurology
Evangelos Pavlos Myserlis, Marios K. Georgakis, Stacie L. Demel, Padmini Sekar, Jaeyoon Chung, Rainer Malik, Hyacinth I. Hyacinth, Mary E. Comeau, Guido J. Falcone, Carl D. Langefeld, Jonathan Rosand, Daniel Woo, Christopher D. Anderson
Summary: Researchers developed a genomic risk score that predicts the risk of intracerebral hemorrhage (ICH) in individuals of European ancestry. The score showed better predictive power than standard clinical risk factors and may improve clinical decision making for high-risk populations.
Editorial Material
Multidisciplinary Sciences
Ludovic Orlando
Summary: An extensive genomic time series has been conducted on 356 humans from ice-age Europe, showing the impact of climate change on the migration patterns and cultural development of hunter-gatherer populations.
Editorial Material
Multidisciplinary Sciences
Karen H. Miga
Summary: Since the publication of the human genome in 2001, advancements in sequencing technology have filled in many of the gaps in the original sequence, leading to a deeper knowledge of genome regulation, structure, and function.
Editorial Material
Multidisciplinary Sciences
Conrad O. Iyegbe, Paul F. O'Reilly
Summary: Rare and common genetic variants associated with schizophrenia provide convergent clues about the underlying biology of this complex disorder.
Article
Clinical Neurology
Anne M. McIntosh, Alex W. Wynd, Samuel F. Berkovic
Summary: This study examined the prevalence and risk factors for late seizure recurrence in a cohort of patients who underwent anterior temporal lobectomy (ATL). The results showed that some patients may experience seizure recurrence several decades after surgery, and this late recurrence is not unique to any specific pathology group and does not differ based on the surgical approach.
Article
Genetics & Heredity
Takuya Hiraide, Tenpei Akita, Kenji Uematsu, Sachiko Miyamoto, Mitsuko Nakashima, Masayuki Sasaki, Atsuo Fukuda, Mitsuhiro Kato, Hirotomo Saitsu
Summary: This study reports a case of KCNB1 mutation that results in a milder phenotype compared to previously reported cases. The brain MRI of the patient showed characteristic abnormalities, and functional analysis revealed that the mutant variant reduces channel activation and inactivation at specific membrane voltages.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Mitsuko Nakashima, Emanuela Argilli, Sayaka Nakano, Elliott H. Sherr, Mitsuhiro Kato, Hirotomo Saitsu
Summary: A recent study discovered that genetic variants in the CLCN3 gene can cause neurodevelopmental disorders and brain abnormalities. The study found that some variants had a gain-of-function effect on channel activity. Two patients with specific CLCN3 variants showed severe neurological symptoms and a range of brain abnormalities. These findings expand our understanding of CLCN3-related disorders.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Clinical Neurology
Kaoru Yamamoto, Shimpei Baba, Takashi Saito, Eiji Nakagawa, Kenji Sugai, Masaki Iwasaki, Atsushi Fujita, Hiromi Fukuda, Takeshi Mizuguchi, Mitsuhiro Kato, Naomichi Matsumoto, Masayuki Sasaki
Summary: Suppression-burst (SB) is an EEG pattern observed in DEEs, which are associated with high mortality in early life. This study investigated the relation between SB-EEG and autonomic function in DEEs to explore the mechanism of early death. The results showed that patients with KCNT1-DEE exhibited synchronous HR fluctuations during SB-EEG, with a decrease in HR during suppression and an increase during burst. Patients with KCNT1-DEE had larger HR decreases and longer suppression durations compared to other patients. A strong negative correlation was found between suppression duration and HR reduction rates in one patient with KCNT1-DEE.
Article
Clinical Neurology
Russell Nightscales, Sarah Barnard, Juliana Laze, Zhibin Chen, Gerard Tao, Clarissa Auvrez, Shobi Sivathamboo, Mark J. Cook, Patrick Kwan, Daniel Friedman, Samuel F. Berkovic, Wendyl D'Souza, Piero Perucca, Orrin Devinsky, Terence J. O'Brien
Summary: This study aimed to investigate the association between lamotrigine and sudden unexpected death in epilepsy (SUDEP). The retrospective, nested case-control study included 101 SUDEP cases and 199 living epilepsy controls from Australia and the USA. The results showed no increased risk of SUDEP associated with the use of lamotrigine or other sodium channel modulating anti-seizure medications.
Article
Neurosciences
Matthew J. Y. Kang, Dhamidhu Eratne, Hannah Dobson, Charles B. B. Malpas, Michael Keem, Courtney Lewis, Jasleen Grewal, Vivian Tsoukra, Christa Dang, Ramon Mocellin, Tomas Kalincik, Alexander F. F. Santillo, Henrik Zetterberg, Kaj Blennow, Christiane Stehmann, Shiji Varghese, Qiao-Xin Li, Colin L. L. Masters, Steven Collins, Samuel F. Berkovic, Andrew Evans, Wendy Kelso, Sarah Farrand, Samantha M. M. Loi, Mark Walterfang, Dennis Velakoulis
Summary: CSF NfL shows promise in accurately diagnosing neuropsychiatric symptoms and distinguishing between neurodegenerative disorders and psychiatric disorders. It improves diagnostic accuracy compared to clinical assessment alone.
ACTA NEUROPSYCHIATRICA
(2023)
Article
Clinical Neurology
Cinzia Costa, Karen L. Oliver, Carmen Calvello, Jillian M. Cameron, Valentina Imperatore, Laura Tonelli, Davide Colavito, Silvana Franceschetti, Laura Canafoglia, Samuel F. Berkovic, Paolo Prontera
Summary: Progressive myoclonus epilepsies (PMEs) are a diverse group of neurodegenerative disorders that typically occur in late childhood. Through genome-wide molecular studies, pathogenic variants in the IRF2BPL gene were identified in patients with PME, suggesting its involvement in the disease. These findings expand the phenotypic spectrum of IRF2BPL-related disorders and highlight the importance of considering this gene in the diagnosis of patients with PME.
Article
Clinical Neurology
Jillian M. Cameron, John A. Damiano, Bronwyn Grinton, Patrick W. Carney, Penny McKelvie, Peter Silbert, Nicholas Lawn, Ingrid E. Scheffer, Karen L. Oliver, Michael S. Hildebrand, Samuel F. Berkovic
Summary: This study analyzed the phenotypic features of a group of patients with protracted CLN3 disease in order to improve recognition of the disorder. The results showed that visual impairment was the initial symptom, with onset at 5-9 years, similar to classic CLN3 disease. The disease is often accompanied by progressive generalized and focal seizures.
Article
Clinical Neurology
Richard Bagnall, Piero Perucca, ILAE Genetics Commission
Summary: A 24-year-old man with non-lesional bitemporal lobe epilepsy was found dead in bed. His death was classified as sudden unexpected death in epilepsy (SUDEP). The family is seeking answers regarding the cause of death and the risk for other family members, prompting the consideration of postmortem genetic testing. While there is uncertainty about the genetic contributions to SUDEP, this article aims to explore the topic and provide insights into this clinically important area.
EPILEPTIC DISORDERS
(2023)
Article
Clinical Neurology
Charissa Millevert, Sarah Weckhuysen, ILAE Genetics Commission
Summary: This article summarizes the self-limited (familial) epilepsies with onset in neonates or infants, which are autosomal dominant disorders characterized by focal motor seizures in the neonatal or infantile period and the absence of neurodevelopmental complications. The seizures tend to remit during infancy or early childhood, hence the term "self-limited". A positive family history suggests the genetic etiology, but incomplete penetrance and de novo inheritance can occur. The article reviews the phenotypic spectrum, genetic architecture, diagnostic steps, management, and genetic counseling of these syndromes through a case study.
EPILEPTIC DISORDERS
(2023)
Article
Clinical Neurology
Jacob Pellinen, Heath Pardoe, Stefan Sillau, Sarah Barnard, Jacqueline French, Robert Knowlton, Daniel D. Lowenstein, Gregory Cascino, Simon Glynn, Graeme Jackson, Jerzy Szaflarski, Chris J. Morrison, Kimford Meador, Ruben Kuzniecky, Human Epilepsy Project Investigators
Summary: This study found that people with newly treated focal epilepsy and learning difficulties have lower brain tissue volume to intracranial volume, suggesting that developmental factors are an important marker of neuroanatomical changes in focal epilepsy. There were also independent associations between brain volume, age, and sex in the study population.
Article
Clinical Neurology
James Allebone, Richard A. Kanaan, Genevieve Rayner, Jerome Maller, Terence J. O'Brien, Saul A. Mullen, Mark Cook, Sophia J. Adams, Simon Vogrin, David N. Vaughan, Patrick Kwan, Samuel F. Berkovic, Wendyl J. D'Souza, Graeme Jackson, Dennis Velakoulis, Sarah J. Wilson
Summary: Patients with psychosis of epilepsy showed reduced performance in neuropsychological functions supported by the default mode and cognitive control networks.
Review
Clinical Neurology
Jillian M. Cameron, Colin A. Ellis, Samuel F. Berkovic, ILAE Genetics Commiss, ILAE Genetic Literacy Task Force
Summary: Progressive Myoclonus Epilepsy (PME) is a rare epilepsy syndrome characterized by worsening myoclonus, ataxia, and seizures. Molecular diagnosis can be established in 80% of PME cases, with nearly fifty genetic causes identified. This review provides a comprehensive understanding of the clinical phenotypes, genotypes, and management strategies for PME, using a case example to illustrate the approaches.
EPILEPTIC DISORDERS
(2023)
Article
Education, Scientific Disciplines
Deanna Wai-Ching Lee, Choon Kiat Nigel Tan, Kevin Tan, Xianguang Joel Yee, Yasmin Jion, Herma Roebertsen, Chaoyan Dong
Summary: The development of Educator Identity has a significant impact on well-being, motivation, productivity, and the quality of teaching. Personal, relational, and organizational factors were found to influence the development of Clinical Educator Identity, with relational aspect being a vital enabler and organizational culture being a strong barrier. The study also provides guidance on how organizations can support Educator Identity development.
