Article
Clinical Neurology
Abolfazl Yari, Reza Molla Ali-Nejad, Nasrollah Saleh-Gohari
Summary: This study identified a homozygous splicing c.423+1 G>A variant in the SCARB2 gene in an Iranian family with two affected individuals, suggesting a potential pathogenic role in causing progressive myoclonic epilepsy-4. The variant was not found in genetic databases, predicted to affect the 5' donor splice site, and classified as a likely pathogenic variant according to ACMG standards and guidelines.
NEUROLOGICAL SCIENCES
(2021)
Article
Medicine, General & Internal
Hakan Ekmekci, Omar Qutob, Huseyn Babayev, Ali Sahin
Summary: Action myoclonus-renal failure (AMRF) syndrome is a rare autosomal recessive disorder characterized by myoclonic epilepsy with occasional renal failure comorbidity. This study examines a consanguineous family with multiple members presenting myoclonic epilepsy. The disease's continued transmission within the family is attributable to a lack of genetic testing and the inability to establish a definitive diagnosis.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Genetics & Heredity
Chen Pan, Jun Li, Shixin Wang, Chen Shi, Yunmei Zhang, Yafeng Yu
Summary: This report presents a case of novel heterozygous mutations in the OTOGL gene causing mild sensorineural hearing loss. Two novel mutations were identified through whole exome sequencing and Sanger sequencing, enriching the mutation spectrum of OTOGL and providing a foundation for gene function research and genetic counseling.
Article
Multidisciplinary Sciences
Takeshi Kawakami, Vandana Raghavan, Alison L. Ruhe, Meghan K. Jensen, Ausra Milano, Thomas C. Nelson, Adam R. Boyko
Summary: This study identified a genomic region and a specific genetic mutation associated with early onset adult deafness (EOAD) in Rhodesian Ridgebacks, providing valuable insights for understanding hearing disorders in both dogs and humans.
Article
Medicine, General & Internal
Pavlina Plevova, Jana Indrakova, Judy Savige, Petra Kuhnova, Petra Tvrda, Dita Cerna, Sarka Hilscherova, Monika Kudrejova, Daniela Polendova, Radka Jaklova, Martina Langova, Helena Jahnova, Jana Lastuvkova, Jiri Dusek, Josef Gut, Marketa Vlckova, Pavla Solarova, Gabriela Kreckova, Eva Kantorova, Jana Soukalova, Rastislav Slavkovsky, Jana Zapletalova, Tomas Tichy, Dana Thomasova
Summary: This study found two gene variants in the Romani population that contribute to the high prevalence of kidney failure. These variants are involved in Alport syndrome, a common genetic kidney disease characterized by hematuria, proteinuria, end-stage kidney failure, hearing loss, and eye anomalies. These findings have important implications for the prevention and treatment of kidney diseases in the Romani population.
FRONTIERS IN MEDICINE
(2023)
Article
Health Care Sciences & Services
Tatiana Markova, Natalia Alekseeva, Maria Lalayants, Oxana Ryzhkova, Olga Shatokhina, Nailya Galeeva, Elena Bliznetz, Oleg Belov, Svetlana Chibisova, Alexander Polyakov, George Tavartkiladze
Summary: Congenital and early onset bilateral sensorineural hearing loss (SNHL) is mainly caused by mutations in numerous genes. The presence of at least one GJB2 non-truncating variant leads to less severe hearing impairment, with flat and gently sloping audiogram profiles mostly revealed in all groups. Follow-up showed stability of hearing thresholds, with GJB2, STRC, and USH2A pathogenic variants being congenital in most cases.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Multidisciplinary Sciences
Nobuyoshi Tsuzuki, Koichiro Wasano, Naoki Oishi, Ko Hentona, Marie Shimanuki, Takanori Nishiyama, Yoshihiko Hiraga, Seiichi Shinden, Kaoru Ogawa
Summary: The study aimed to investigate the association between idiopathic sudden sensorineural hearing loss (idiopathic SSNHL) and stroke risk in patients, suggesting that circulatory disorders may be a primary cause of severe idiopathic SSNHL in individuals at high risk of stroke. The results indirectly supported the hypothesis by showing a significantly lower rate of vestibular schwannoma (VS) in high-stroke-risk patients with severe hearing loss compared to low-stroke-risk individuals.
SCIENTIFIC REPORTS
(2021)
Review
Clinical Neurology
Burcu Atasu, Ayse Nur Ozdag Acarli, Basar Bilgic, Betul Baykan, Erol Demir, Yasemin Ozluk, Aydin Turkmen, Ann-Kathrin Hauser, Gamze Guven, Hasmet Hanagasi, Hakan Gurvit, Murat Emre, Thomas Gasser, Ebba Lohmann
Summary: This study shows that biallelic pathogenic variants in the SCARB2 gene can cause a spectrum of features associated with AMRF. Common features include myoclonus, ataxia, seizures, dysarthria, tremor, and renal impairment, while uncommon features involve peripheral neuropathy, hearing loss, and cognitive impairment. The C terminal localization of the pathogenic variant significantly affects the age at onset of the disease.
Article
Health Care Sciences & Services
Gema Esteban-Bueno, Aida Maria Berenguel Hernandez, Nicolas Fernandez Fernandez, Miguel Navarro Cabrero, Juan R. Coca
Summary: Wolfram syndrome (WS) is a rare neurodegenerative disease with autosomal recessive origin. Limited research on sensorineural hearing loss in WS has been conducted. It is important to conduct further studies and establish a set of tests for accurate assessment, monitoring, and control of patients. The objective of this research is to understand WS biomedically and aid in diagnosis and treatment. Audiological measurements such as pure tones audiometry, tympanometry, speech perception, and high-frequency testing were utilized for standardized follow-up. Mixed linear models were used to examine the effects of age and time on various hearing measurements. Genetic analysis revealed phenotype-genotype groups, indicating the severity of hearing loss. Early detection of sensorineural hearing loss and WS is crucial for intensive follow-up and treatment.
Article
Genetics & Heredity
Baoling Kang, Xinshu Lu, Jianjun Xiong, Yuan Li, Jinwen Zhu, Tao Cai
Summary: In this study, four compound heterozygous variants in the CDH23 gene were identified through whole-exome sequencing. These variants may serve as potential genetic causes for hearing loss. The findings significantly expand the mutation spectrum of CDH23-associated hearing loss.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Guangxian Yang, Yi Yin, Zhiping Tan, Jian Liu, Xicheng Deng, Yifeng Yang
Summary: This study identified a Chinese family with both TBS and hearing loss, and detected genetic mutations through whole-exome sequencing and Sanger sequencing. The findings confirmed the molecular diagnosis of TBS and expanded the spectrum of SALL1 and PTPRQ mutations, potentially contributing to clinical management and genetic counseling for these conditions.
BMC MEDICAL GENOMICS
(2021)
Article
Audiology & Speech-Language Pathology
Guadalupe G. San Miguel, Karen Munoz, Tyson S. Barrett, Michael P. Twohig
Summary: The purpose of this study was to validate the AAQ-AHL and the results suggest that it is a valid instrument to assess psychological flexibility as it relates to hearing aid use.
INTERNATIONAL JOURNAL OF AUDIOLOGY
(2023)
Article
Genetics & Heredity
Mehdi Dianatpour, Emily Smith, Seyed Basir Hashemi, Mohammad A. Farazifard, Navid Nezafat, Vahid Razban, Arya Mani
Summary: In this study, genetic screening was carried out on ten Iranian kindreds affected by ARNSD caused by consanguineous unions, identifying the disease causing genes and revealing novel pathogenic mutations through whole exome sequencing. This study expands the spectrum of genes contributing to ARNSD in the Iranian population.
Article
Geriatrics & Gerontology
Julien F. Bally, Ming Zhang, Emily Dwosh, Christine Sato, John Rutka, Anthony E. Lang, Ekaterina Rogaeva
Summary: This study conducted a genetic analysis of a rare Dutch-Canadian family and found that hearing loss and balance problems are associated with a mutation in the COCH gene, while action tremor is related to a rare mutation in the MCM9 gene. These novel findings suggest a potential association between the MCM9 gene and action tremor, warranting further investigation.
NEUROBIOLOGY OF AGING
(2022)
Article
Otorhinolaryngology
Zhijie Niu, Lingyun Mei, Fen Tang, Jiada Li, Xueping Wang, Jie Sun, Chufeng He, Hongsheng Cheng, Yalan Liu, Xinzhang Cai, Jian Song, Yong Feng, Lu Jiang
Summary: This study investigated the genetic cause of hearing loss in a Chinese WS1 family, identifying a novel missense mutation in the PAX3 gene and revealing the functional consequences of the mutation. The findings suggest haploinsufficiency may be the underlying mechanism for the WS1 phenotype.
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY
(2021)
Article
Pediatrics
Zeeshan Shaukat, Roger W. Byard, Robert Vink, Rashid Hussain, Michael G. Ricos, Leanne M. Dibbens
Summary: Sudden infant death syndrome (SIDS) occurs more frequently in male infants, potentially involving the X-chromosome and altered expression of the Neurokinin-1 receptor. This study aimed to identify genetic variants in three X-chromosome-encoded microRNAs (miRNAs) that down-regulate the Neurokinin-1 receptor and determine if there is a difference in frequency between male and female SIDS cases. No novel variants were found in the miRNAs, only one known single-nucleotide polymorphism (SNP) in miR320D2, with no significant difference in frequency observed between male and female SIDS cases. This pilot study suggests that these three miRNA variants do not contribute to the higher prevalence of SIDS in male infants nor the pathogenesis of SIDS in the study cohort.
Article
Clinical Neurology
Piero Perucca, Kate Stanley, Natasha Harris, Anne M. McIntosh, Ali A. Asadi-Pooya, Mohamad A. Mikati, Danielle M. Andrade, Patricia Dugan, Chantal Depondt, Hyunmi Choi, Erin L. Heinzen, Gianpiero L. Cavalleri, Russell J. Buono, Orrin Devinsky, Michael R. Sperling, Samuel F. Berkovic, Norman Delanty, David B. Goldstein, Terence J. O'Brien
Summary: This study investigated whether rare genetic variations influence seizure outcomes of MTLE surgery. The results showed that MTLE cases carried a higher burden of ultrarare missense variants in constrained genes and genes encoding voltage-gated cation channels. However, these genetic variations did not have a major role in the failure of MTLE surgery.
ANNALS OF NEUROLOGY
(2023)
Article
Clinical Neurology
Samuel F. Berkovic, Pasquale Striano, Shoji Tsuji
Summary: Familial adult myoclonus epilepsy/benign adult familial myoclonic epilepsy (FAME/BAFME) is a specific and recognizable epilepsy syndrome with autosomal dominant inheritance. Initially, it was confused with other familial myoclonus epilepsies but was later recognized as a distinct syndrome in Japan. Families with this syndrome were subsequently identified worldwide, and it was found to be caused by pentanucleotide expansions in at least six genes. The phenotype varies within and between families, mainly due to expansion size.
Article
Behavioral Sciences
Anne M. McIntosh, Patrick W. Carney, K. Meng Tan, Tahir M. Hakami, Piero Perucca, Patrick Kwan, Terence J. O'Brien, Samuel F. Berkovic
Summary: Individuals with epilepsy often have comorbid medical and psychiatric conditions, which are associated with poor epilepsy outcomes. This study examined pre-existing conditions in patients with new diagnoses of epilepsy or unprovoked seizures and found high prevalence of psychiatric and substance use disorders. The findings highlight the importance of screening and managing comorbidities in individuals with epilepsy.
EPILEPSY & BEHAVIOR
(2023)
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
Sattar Khoshkhoo, Yilan Wang, Yasmine Chahine, E. Zeynep Erson-Omay, Stephanie M. Robert, Emre Kiziltug, Eyiyemisi C. Damisah, Carol Nelson-Williams, Guangya Zhu, Wenna Kong, August Yue Huang, Edward Stronge, H. Westley Phillips, Brian H. Chhouk, Sara Bizzotto, Ming Hui Chen, Thiuni N. Adikari, Zimeng Ye, Tom Witkowski, Dulcie Lai, Nadine Lee, Julie Lokan, Ingrid E. Scheffer, Samuel F. Berkovic, Shozeb Haider, Michael S. Hildebrand, Edward Yang, Murat Gunel, Richard P. Lifton, R. Mark Richardson, Ingmar Bluemcke, Sanda Alexandrescu, Anita Huttner, Erin L. Heinzen, Jidong Zhu, Annapurna Poduri, Nihal DeLanerolle, Dennis D. Spencer, Eunjung Alice Lee, Christopher A. Walsh, Kristopher T. Kahle
Summary: This study found pathogenic somatic variants in the hippocampus of patients with drug-resistant temporal lobe epilepsy, suggesting their association with the disease pathogenesis. These findings offer new insights into the genetic mechanisms and potential therapeutic targets for this common type of epilepsy.
Article
Biochemistry & Molecular Biology
Anowarul Islam, Zeeshan Shaukat, David L. Newman, Rashid Hussain, Michael G. Ricos, Leanne Dibbens, Stephen L. Gregory
Summary: Aneuploidy, a disrupted genome commonly found in tumors, causes proteotoxic stress and oxidative shift, making cells sensitive to stresses. Studying Drosophila, changes in transcription due to ongoing changes to ploidy (chromosomal instability, CIN) were investigated. Genes involved in one-carbon metabolism, specifically SAM production and use, were found to affect cell death in CIN cells. Inhibiting polyamine metabolism rescued cell death, indicating a potential metabolic intervention for targeting CIN tumors.
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)
Review
Neurosciences
Timothy E. Green, Atsushi Fujita, Navid Ghaderi, Erin L. Heinzen, Naomichi Matsumoto, Karl Martin Klein, Samuel F. Berkovic, Michael S. Hildebrand
Summary: Hypothalamic hamartoma (HH) is a rare brain lesion associated with a specific epilepsy phenotype. Most patients have no additional developmental anomalies or family history of the disease. It has been discovered that some patients with HH have post-zygotic mosaic variants in genes related to Shh signaling and cilia development and function, providing insights into the functional role of these genes.
NEUROBIOLOGY OF DISEASE
(2023)
