Article
Biochemistry & Molecular Biology
Lucia Pia Bruno, Gabriella Doddato, Floriana Valentino, Margherita Baldassarri, Rossella Tita, Chiara Fallerini, Mirella Bruttini, Caterina Lo Rizzo, Maria Antonietta Mencarelli, Francesca Mari, Anna Maria Pinto, Francesca Fava, Alessandra Fabbiani, Vittoria Lamacchia, Anna Carrer, Valentina Caputo, Stefania Granata, Elisa Benetti, Kristina Zguro, Simone Furini, Alessandra Renieri, Francesca Ariani
Summary: Intelectual disability (ID) and autism spectrum disorder (ASD) are often associated and characterized by impairments in cognitive processes and daily life tasks. Molecular diagnosis is crucial for improving prognosis and initiating treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Julia Horjus, Tineke van Mourik-Banda, Marco A. P. Heerings, Marina Hakobjan, Ward De Witte, Dorothea J. Heersema, Anne J. Jansen, Eva M. M. Strijbis, Brigit A. de Jong, Astrid E. J. Slettenaar, Esther M. P. E. Zeinstra, Erwin L. J. Hoogervorst, Barbara Franke, Wiebe Kruijer, Peter J. Jongen, Leo J. Visser, Geert Poelmans
Summary: This study identified 12 rare genetic variants associated with multiple sclerosis through whole exome sequencing and co-segregation analysis, highlighting the involvement of various biological processes related to (de-/re-)myelination and auto-immunity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Raffaele Gaeta, Mariangela Morelli, Francesca Lessi, Chiara Maria Mazzanti, Michele Menicagli, Rodolfo Capanna, Lorenzo Andreani, Luca Coccoli, Paolo Aretini, Alessandro Franchi
Summary: This study aims to identify gene alterations in high-grade osteosarcoma (OS) patients using whole exome sequencing (WES) to find new potential prognostic biomarkers and therapeutic targets. Mutations in ARID1A, CREBBP, BRCA2 and RAD50 genes were found to be significantly correlated with poor response to neoadjuvant therapy and negatively influenced the progression-free survival time. Moreover, higher tumor mutational burden values were associated with worse prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Rotem Tal-Ben Ishay, Apurba Shil, Shirley Solomon, Noa Sadigurschi, Hadeel Abu-Kaf, Gal Meiri, Hagit Flusser, Analya Michaelovski, Ilan Dinstein, Hava Golan, Nadav Davidovitch, Idan Menashe
Summary: WES is an effective approach to identify the susceptibility of genetic variants of autism spectrum disorder (ASD). This study applied WES to a population-based sample of Bedouin and Jewish children with ASD in southern Israel, and found a diagnostic yield of 15.4%. The most cost-effective genetic testing method was chromosomal microarray analysis (CMA).
Article
Neurosciences
Bo Yuan, Mengdi Wang, Xinran Wu, Peipei Cheng, Ran Zhang, Shunying Yu, Jie Zhang, Yasong Du, Xiaoqun Wang, Zilong Qiu
Summary: In this study, whole-exome sequencing was used to examine Chinese individuals with autism spectrum disorder (ASD) and their parents. The researchers identified a large number of de novo mutations and copy number variations related to ASD. They also found that genes with these de novo mutations were specifically expressed in certain regions of the human brain, and that ASD patients had structural and functional abnormalities in these brain regions.
NEUROSCIENCE BULLETIN
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Yunsun Song, Jong-Keuk Lee, Jin-Ok Lee, Boseong Kwon, Eul-Ju Seo, Dae Chul Suh
Summary: Using whole exome sequencing, rare, potentially deleterious variants in the PLOD3, NTM, and CHST14 genes were identified as likely responsible for subsets of familial intracranial aneurysms in a cohort of Korean families. These variants were selected from families with a genetic enrichment for intracranial aneurysms.
KOREAN JOURNAL OF RADIOLOGY
(2022)
Article
Health Care Sciences & Services
Jeffery L. Clothier, Amy N. Grooms, Patricia A. Porter-Gill, Pritmohinder S. Gill, G. Bradley Schaefer
Summary: This study reports a case of a 32-year-old male patient who was diagnosed with Cornelia De Lange Syndrome (CDLS) in infancy and later with autism and intellectual disability. Genetic and methylation studies identified a de novo variant in the DCAF1 gene, which is associated with autism and intellectual disability. This study provides new insights into the genetic basis of ASD.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Medicine, General & Internal
Taylor B. Cavazos, Linda Kachuri, Rebecca E. Graff, Jovia L. Nierenberg, Khanh K. Thai, Stacey Alexeeff, Stephen Van den Eeden, Douglas A. Corley, Lawrence H. Kushi, Regeneron Genetics Center, Thomas J. Hoffmann, Elad Ziv, Laurel A. Habel, Eric Jorgenson, Lori C. Sakoda, John S. Witte
Summary: This study conducted whole-exome sequencing of individuals from two large multi-ancestry populations to characterize genetic susceptibility to multiple cancers, identifying variants and genes that may play a fundamental role in the development of multiple primary cancers. The results suggest shared mechanisms underlying carcinogenesis and highlight previously undiscovered variant-phenotype associations significantly overrepresented among individuals with multiple cancers.
Article
Neurosciences
Phan Q. Duy, Andrew T. Timberlake, Richard P. Lifton, Kristopher T. Kahle
Summary: Recent trio-based whole-exome sequencing studies have identified multiple novel disease genes associated with congenital hydrocephalus and nonsyndromic craniosynostosis, providing new insights into the pathogenesis of these disorders and the genetic regulation of human brain and skull development. Further research into these and other understudied developmental anomalies has the potential to improve precision in genetic counseling, prognostication, and surgical treatment strategies by replacing the current anatomically based disease classification systems with a molecular nomenclature.
Article
Genetics & Heredity
Pietro Palumbo, Ester Di Muro, Maria Accadia, Mario Benvenuto, Marilena Carmela Di Giacomo, Stefano Castellana, Tommaso Mazza, Marco Castori, Orazio Palumbo, Massimo Carella
Summary: Neurodevelopmental disorders (NDDs) are a group of disorders affecting children, with AUTS2 gene being one of the implicated genes. This study presents a case of a 9-year-old boy carrying a deletion mutation in AUTS2, expanding the understanding of its pathogenic variants.
Review
Clinical Neurology
Arthur Stefanski, Yamile Calle-Lopez, Costin Leu, Eduardo Perez-Palma, Elia Pestana-Knight, Dennis Lal
Summary: This meta-analysis and systematic review examined the diagnostic yield of clinical sequencing studies in individuals with neurodevelopmental disorders, finding differences in success rates across NDD subtypes and sequencing technologies. Studies were predominantly conducted in countries with a high Inequality-adjusted Human Development Index, with potential barriers to genetic testing in regions like Africa, India, and Latin America.
Article
Health Care Sciences & Services
Yingzhao Huang, Bowen Liu, Jile Shi, Sen Zhao, Kexin Xu, Liying Sun, Na Chen, Wen Tian, Jianguo Zhang, Nan Wu
Summary: Clinical exome sequencing has proven to be useful in diagnosing Mendelian disorders and can reveal secondary findings unrelated to the primary diagnosis. This study evaluated genetic data from 2987 individuals in the Chinese population and found that 5.3% of them had reportable variants associated with cancer, cardiovascular, metabolic, and other phenotypes. Additionally, 1.5% of the individuals carried secondary findings in newly added genes.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Ophthalmology
Entuan Yang, Jifeng Yu, Xue Liu, Huihui Chu, Li Li
Summary: This study identified potential pathogenic genes associated with early-onset high myopia (eoHM) using whole-exome sequencing. Five genes and ten loci associated with eoHM were identified, and a high presence of genes associated with retinal diseases was found in the 30 families. The study also revealed a correlation between candidate genes and fundus photography phenotype.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Genetics & Heredity
Kiran Narta, Manoj Ramesh Teltumbade, Mansi Vishal, Samreen Sadaf, Mohd. Faruq, Hodan Jama, Naushin Waseem, Aparna Rao, Abhijit Sen, Kunal Ray, Arijit Mukhopadhyay
Summary: This study identifies novel genes and gene networks associated with familial forms of primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) through whole-exome sequencing and analysis. Rare mutations with high penetrance were found in glaucoma cases, and the expression profiles of candidate genes were analyzed. The study provides insights into the genetic mechanisms of glaucoma.
Article
Neurosciences
Felipe Franco da Graca, Thiago M. Peluzzo, Luciana Cardoso Bonadia, Alberto Rolim Muro Martinez, Fabricio Diniz de Lima, Jose Luiz Pedroso, Orlando G. P. Barsottini, Maria Thereza Drummond Gama, Fulya Akcimen, Patrick A. Dion, Guy A. Rouleau, Wilson Marques, Marcondes Cavalcante Franca Jr
Summary: This study used whole exome sequencing to investigate a Brazilian cohort of adult patients with ataxia, and found a diagnostic yield of 35.5%, with mutations in 20 different genes responsible for autosomal recessive and dominant ataxias. SACS and SPG7 were the most frequently identified underlying genes. The diagnostic performance of WES was significantly better in the subgroup with spasticity compared to the subgroup without spasticity.
Article
Allergy
Nicolas Giang, Marion Mars, Marc Moreau, Jose E. Mejia, Gregory Bouchaud, Antoine Magnan, Marine Michelet, Brice Ronsin, Geoffrey G. Murphy, Joerg Striessnig, Jean-Charles Guery, Lucette Pelletier, Magali Savignac
Summary: This study demonstrates that Ca(v)1.2 and Ca(v)1.3 in Th2 cells have non-redundant and synergistic functions, and deficiency in either one of these channels is sufficient to inhibit cardinal features of type 2 airway inflammation.
Correction
Chemistry, Physical
Maren Podewitz, Yin Wang, Paraskevi Gkeka, Susanne von Grafenstein, Klaus R. Liedl, Zoe Cournia
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Inorganic & Nuclear
Reinhard Thaler, Holger Kopacka, Klaus Wurst, Thomas Mueller, Dennis F. Dinu, Klaus R. Liedl, Florian R. Neururer, Stephan Hohloch, Benno Bildstein
Summary: This article reports on the synthesis and properties of boron-substituted tromancenium salts, revealing their potential for novel synthetic applications.
Correction
Biochemistry & Molecular Biology
Monica L. Fernandez-Quintero, Patrick K. Quoika, Florian S. Wedl, Clarissa A. Seidler, Katharina B. Kroell, Johannes R. Loeffler, Nancy D. Pomarici, Valentin J. Hoerschinger, Alexander Bujotzek, Guy Georges, Hubert Kettenberger, Klaus R. Liedl
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Multidisciplinary Sciences
Josef Shin, Lora Kovacheva, Dominique Thomas, Strahinja Stojanovic, Christopher J. Knowlton, Johanna Mankel, Johannes Boehm, Navid Farassat, Carlos Paladini, Joerg Striessnig, Carmen C. Canavier, Gerd Geisslinger, Jochen Roeper
Summary: This study reveals the pacemaker function of the low-threshold L-type calcium channel Ca(v)1.3 in mice and demonstrates its role as a linear amplifier of firing rates for neuronal activity. It also provides evidence that the L-type channel inhibitor isradipine can selectively reduce the firing activity of vulnerable nigrostriatal DA SN neurons at therapeutic concentrations. These findings have important implications for the treatment of Parkinson's disease.
Article
Biochemistry & Molecular Biology
Ferenc Torok, Kamer Tezcan, Ludovica Filippini, Monica L. Fernandez-Quintero, Lucia Zanetti, Klaus R. Liedl, Raphaela S. Drexel, Joerg Striessnig, Nadine J. Ortner
Summary: Germline gain-of-function missense variants in the CACNA1D gene can cause severe neurodevelopmental disorders with or without endocrine symptoms. We report a 4-week-old newborn with a novel de novo missense variant F747S in the Cav1.3 alpha 1-subunit, which is associated with a prominent jittering phenotype, developmental delay, elevated aldosterone level, and transient hypoglycemia. Functional experiments confirmed the pathogenicity of the variant and revealed significant changes in channel gating. The increased sensitivity to the L-type Ca2+ channel blocker isradipine suggests its potential as a treatment option for carriers of this mutation.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Rafael Eduardo Oliveira Rocha, Diego Cesar Batista Mariano, Tiago Silva Almeida, Leon Sulfierry CorreaCosta, Pedro Henrique Camargo Fischer, Lucianna Helene Santos, Ernesto Raul Caffarena, Carlos Henrique da Silveira, Leonida M. Lamp, Monica Lisa Fernandez-Quintero, Klaus Roman Liedl, Raquel Cardoso De Melo-Minardi, Leonardo Henrique Franca de Lima
Summary: In this study, the molecular basis of the thermostabilization of the Paenibacillus polymyxa GH1 beta-glucosidase by two-point mutations was investigated through molecular dynamics simulations and computational analyses. Three classic mechanisms were found to contribute to the stabilization of the thermostable mutants.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Susanne Rinne, Birgit Stallmeyer, Alexandra Pinggera, Michael F. Netter, Lina A. Matschke, Sven Dittmann, Uwe Kirchhefer, Ulrich Neudorf, Joachim Opp, Joerg Striessnig, Niels Decher, Eric Schulze-Bahr
Summary: Cav1.3 voltage-gated L-type calcium channels are associated with various clinical symptoms, such as cardiac pacemaking, hearing, hormone secretion, epilepsy, autism, intellectual disability, and ADHD. This study identified a genetic variant in the CACNA1D gene that was associated with a syndromal phenotype of sinus node dysfunction, epilepsy, and ADHD in a three-generation family. Functional studies revealed that the variant induced isoform-specific alterations in Cav1.3 channel function, leading to the combined clinical symptoms observed in the family.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Ludovica Filippini, Nadine J. J. Ortner, Teresa Kaserer, Jorg Striessnig
Summary: Voltage-gated L-type Ca2+-channels, especially Ca(v)1.3 subtype, are potential drug targets for the treatment of various diseases. However, the selectivity of Ca(v)1.3-selective blockers remains controversial, and there are no suitable pharmacological tools to confirm or refute the role of Ca(v)1.3 channels in cellular responses. Essential criteria for a small molecule to be considered Ca(v)1.3-selective are suggested.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Clarissa A. Seidler, Janik Kokot, Monica L. Fernandez-Quintero, Klaus R. Liedl
Summary: In this study, the conformational diversity of four VHH variants and their binding to hen egg-white lysozyme (HEL) were investigated. It was found that with an increase in affinity, the stability of the VHH structure increased and the residues contributing to antigen binding underwent significant changes. In addition, it was observed that the investigated nanobodies followed the conformational selection paradigm, with the binding competent conformation pre-existing within the structural ensembles without the presence of the antigen.
Article
Biochemistry & Molecular Biology
Nancy D. Pomarici, Roberta Cacciato, Janik Kokot, Monica L. Fernandez-Quintero, Klaus R. Liedl
Summary: This study investigates the evolution of immunoglobulin isotypes, highlighting the preserved features and the parts that have mutated over time. Coupled residues in the evolution process are crucial for maintaining the immunoglobulin fold and interactions with other domains. By comparing biophysical properties across different animal classes and isotypes, conserved residues in evolution can be identified. This study offers a general overview of the evolution of immunoglobulin isotypes and advances the understanding of their characteristic biophysical properties for guiding protein design.
Article
Food Science & Technology
Ricarda Zeindl, Annika L. Franzmann, Monica L. Fernandez-Quintero, Clarissa A. Seidler, Valentin J. Hoerschinger, Klaus R. Liedl, Martin Tollinger
Summary: Allergies related to kiwi consumption are on the rise, with cross-reactivity with birch pollen being a major factor. This study determined the three-dimensional structures of PR-10 proteins in kiwi fruits and found that they closely resemble the major allergen in birch pollen. Structural differences were observed compared to another kiwi allergen, Act d 11. Additionally, the study identified the presence of phenolic compound pyrogallol in kiwi proteins.
Article
Allergy
Florian Hofer, Anna-Lena Fischer, Anna S. Kamenik, Franz Waibl, Monica L. Fernandez-Quintero, Klaus R. Liedl
Summary: The profilin allergen family is a class of proteins that are found in plants, viruses, and various eukaryotes. They have a conserved structural fold but exhibit differences in their biophysical properties. In this study, molecular dynamics simulations were performed to investigate the functional differences of three profilin allergens. It was found that these differences are related to conformational flexibility and thermal stability, emphasizing the importance of flexibility in understanding the biophysical differences between structurally similar allergens.
FRONTIERS IN ALLERGY
(2022)
Meeting Abstract
Biophysics
Martin C. Heiss, Monica L. Fernandez-Quintero, Yousra El Ghaleb, Simone Pelizzari, Petronel Tuluc, Marta Campiglio, Klaus R. Liedl, Bernhard E. Flucher
BIOPHYSICAL JOURNAL
(2022)
Review
Neurosciences
Maya Jammoul, Dareen Jammoul, Kevin K. Wang, Firas Kobeissy, Ralph G. Depalma
Summary: This article reviews the possible mechanisms by which traumatic brain injury (TBI) may stimulate the development of opioid use disorder (OUD) and discusses the interaction between these two processes. CNS damage due to TBI appears to drive adverse effects of subsequent OUD, with pain being a risk factor for opioid use after TBI.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Danusa Mar Arcego, Jan-Paul Buschdorf, Nicholas O'Toole, Zihan Wang, Barbara Barth, Irina Pokhvisneva, Nirmala Arul Rayan, Sachin Patel, Euclides Jose de Mendonca Filho, Patrick Lee, Jennifer Tan, Ming Xuan Koh, Chu Ming Sim, Carine Parent, Randriely Merscher Sobreira de Lima, Andrew Clappison, Kieran J. O'Donnell, Carla Dalmaz, Janine Arloth, Nadine Provencal, Elisabeth B. Binder, Josie Diorio, Patricia Pelufo Silveira, Michael J. Meaney
Summary: This study investigates the impact of environmental influences on mental health by integrating transcriptomic data from animal models with human data. The results suggest that hippocampal glucocorticoid-related transcriptional activity mediates the effects of early adversity on neural mechanisms implicated in psychiatric disorders.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Milenna T. van Dijk, Ardesheer Talati, Pratik Kashyap, Karan Desai, Nora C. Kelsall, Marc J. Gameroff, Natalie Aw, Eyal Abraham, Breda Cullen, Jiook Cha, Christoph Anacker, Myrna M. Weissman, Jonathan Posner
Summary: This study found that maternal stress is associated with future depressive symptoms and alterations in microstructure of the dentate gyrus (DG) in offspring. These results were consistent across two independent cohorts.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Josephine C. McGowan, Liliana R. Ladner, Claire X. Shubeck, Juliana Tapia, Christina T. LaGamma, Amanda Anqueira-Gonzalez, Ariana DeFrancesco, Briana K. Chen, Holly C. Hunsberger, Ezra J. Sydnor, Ryan W. Logan, Tzong-Shiue Yu, Steven G. Kernie, Christine A. Denny
Summary: Traumatic brain injury (TBI) leads to fear generalization by altering fear memory traces, and this symptom can be improved with (R,S)-ketamine.
BIOLOGICAL PSYCHIATRY
(2024)