Read by QxMD icon Read


William E Tidyman, Katherine A Rauen
The Ras/mitogen activated protein kinase (MAPK) pathway is essential in the regulation of cell cycle, differentiation, growth, cell senescence and apoptosis, all of which are critical to normal development. A class of neurodevelopmental disorders, RASopathies, is caused by germline mutations in genes of the Ras/MAPK pathway. Through the use of whole exome sequencing and targeted sequencing of selected genes in cohorts of panel-negative RASopathy patients, several new genes have been identified. These include: RIT1, SOS2, RASA2, RRAS and SYNGAP1, that likely represent new, albeit rare, causative RASopathy genes...
September 2016: Current Genetic Medicine Reports
Guhan Ram Venkataraman, Chloe O'Connell, Fumiko Egawa, Dorna Kashef-Haghighi, Dennis P Wall
Autism has been shown to have a major genetic risk component; the architecture of documented autism in families has been over and again shown to be passed down for generations. While inherited risk plays an important role in the autistic nature of children, de novo (germline) mutations have also been implicated in autism risk. Here we find that autism de novo variants verified and published in the literature are Bonferroni-significantly enriched in a gene set implicated in synaptic elimination. Additionally, several of the genes in this synaptic elimination set that were enriched in protein-protein interactions (CACNA1C, SHANK2, SYNGAP1, NLGN3, NRXN1, and PTEN) have been previously confirmed as genes that confer risk for the disorder...
2016: Pacific Symposium on Biocomputing
Martin H Berryer, Bidisha Chattopadhyaya, Paul Xing, Ilse Riebe, Ciprian Bosoi, Nathalie Sanon, Judith Antoine-Bertrand, Maxime Lévesque, Massimo Avoli, Fadi F Hamdan, Lionel Carmant, Nathalie Lamarche-Vane, Jean-Claude Lacaille, Jacques L Michaud, Graziella Di Cristo
Haploinsufficiency of the SYNGAP1 gene, which codes for a Ras GTPase-activating protein, impairs cognition both in humans and in mice. Decrease of Syngap1 in mice has been previously shown to cause cognitive deficits at least in part by inducing alterations in glutamatergic neurotransmission and premature maturation of excitatory connections. Whether Syngap1 plays a role in the development of cortical GABAergic connectivity and function remains unclear. Here, we show that Syngap1 haploinsufficiency significantly reduces the formation of perisomatic innervations by parvalbumin-positive basket cells, a major population of GABAergic neurons, in a cell-autonomous manner...
November 9, 2016: Nature Communications
S Sayols-Baixeras, I Subirana, C Lluis-Ganella, F Civeira, J Roquer, A N Do, D Absher, D Muñoz, C Soriano-Tárraga, J Jiménez-Conde, J Ordovas, M Senti, S Aslibekyan, J Marrugat, D K Arnett, R Elosua
Lipid traits (total, low-density and high-density lipoprotein cholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is an inherited but also modifiable epigenetic mark that has been related to cardiovascular risk factors. Our aim was to identify loci showing differential DNA methylation related to serum lipid levels. Blood DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip. A two-stage epigenome-wide association study was performed, with a discovery sample in the REGICOR study (n=645) and validation in the Framingham Offspring Study (n=2,542)...
September 15, 2016: Human Molecular Genetics
(no author information available yet)
No abstract text is available yet for this article.
October 2016: Journal of Medical Genetics
Cyril J Peter, Laura K Fischer, Marija Kundakovic, Paras Garg, Mira Jakovcevski, Aslihan Dincer, Ana C Amaral, Edward I Ginns, Marzena Galdzicka, Cyralene P Bryce, Chana Ratner, Deborah P Waber, David Mokler, Gayle Medford, Frances A Champagne, Douglas L Rosene, Jill A McGaughy, Andrew J Sharp, Janina R Galler, Schahram Akbarian
BACKGROUND: Early childhood malnutrition affects 113 million children worldwide, impacting health and increasing vulnerability for cognitive and behavioral disorders later in life. Molecular signatures after childhood malnutrition, including the potential for intergenerational transmission, remain unexplored. METHODS: We surveyed blood DNA methylomes (~483,000 individual CpG sites) in 168 subjects across two generations, including 50 generation 1 individuals hospitalized during the first year of life for moderate to severe protein-energy malnutrition, then followed up to 48 years in the Barbados Nutrition Study...
November 15, 2016: Biological Psychiatry
Zhihui Xie, Jing Li, Jonathan Baker, Kathie L Eagleson, Marcelo P Coba, Pat Levitt
BACKGROUND: Atypical synapse development and plasticity are implicated in many neurodevelopmental disorders (NDDs). NDD-associated, high-confidence risk genes have been identified, yet little is known about functional relationships at the level of protein-protein interactions, which are the dominant molecular bases responsible for mediating circuit development. METHODS: Proteomics in three independent developing neocortical synaptosomal preparations identified putative interacting proteins of the ligand-activated MET receptor tyrosine kinase, an autism risk gene that mediates synapse development...
December 15, 2016: Biological Psychiatry
Cyril Mignot, Celina von Stülpnagel, Caroline Nava, Dorothée Ville, Damien Sanlaville, Gaetan Lesca, Agnès Rastetter, Benoit Gachet, Yannick Marie, G Christoph Korenke, Ingo Borggraefe, Dorota Hoffmann-Zacharska, Elżbieta Szczepanik, Mariola Rudzka-Dybała, Uluç Yiş, Hande Çağlayan, Arnaud Isapof, Isabelle Marey, Eleni Panagiotakaki, Christian Korff, Eva Rossier, Angelika Riess, Stefanie Beck-Woedl, Anita Rauch, Christiane Zweier, Juliane Hoyer, André Reis, Mikhail Mironov, Maria Bobylova, Konstantin Mukhin, Laura Hernandez-Hernandez, Bridget Maher, Sanjay Sisodiya, Marius Kuhn, Dieter Glaeser, Sarah Wechuysen, Candace T Myers, Heather C Mefford, Konstanze Hörtnagel, Saskia Biskup, Johannes R Lemke, Delphine Héron, Gerhard Kluger, Christel Depienne
OBJECTIVE: We aimed to delineate the neurodevelopmental spectrum associated with SYNGAP1 mutations and to investigate genotype-phenotype correlations. METHODS: We sequenced the exome or screened the exons of SYNGAP1 in a total of 251 patients with neurodevelopmental disorders. Molecular and clinical data from patients with SYNGAP1 mutations from other centres were also collected, focusing on developmental aspects and the associated epilepsy phenotype. A review of SYNGAP1 mutations published in the literature was also performed...
August 2016: Journal of Medical Genetics
Nallathambi Jeyabalan, James P Clement
A cardinal feature of early stages of human brain development centers on the sensory, cognitive, and emotional experiences that shape neuronal-circuit formation and refinement. Consequently, alterations in these processes account for many psychiatric and neurodevelopmental disorders. Neurodevelopment disorders affect 3-4% of the world population. The impact of these disorders presents a major challenge to clinicians, geneticists, and neuroscientists. Mutations that cause neurodevelopmental disorders are commonly found in genes encoding proteins that regulate synaptic function...
2016: Frontiers in Cellular Neuroscience
Stephanie A Barnes, Lasani S Wijetunge, Adam D Jackson, Danai Katsanevaki, Emily K Osterweil, Noboru H Komiyama, Seth G N Grant, Mark F Bear, U Valentin Nägerl, Peter C Kind, David J A Wyllie
UNLABELLED: Previous studies have hypothesized that diverse genetic causes of intellectual disability (ID) and autism spectrum disorders (ASDs) converge on common cellular pathways. Testing this hypothesis requires detailed phenotypic analyses of animal models with genetic mutations that accurately reflect those seen in the human condition (i.e., have structural validity) and which produce phenotypes that mirror ID/ASDs (i.e., have face validity). We show that SynGAP haploinsufficiency, which causes ID with co-occurring ASD in humans, mimics and occludes the synaptic pathophysiology associated with deletion of the Fmr1 gene...
November 11, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Juan F Codocedo, Carla Montecinos-Oliva, Nibaldo C Inestrosa
Wnt-5a is a synaptogenic factor that modulates glutamatergic synapses and generates neuroprotection against Aβ oligomers. It is known that Wnt-5a plays a key role in the adult nervous system and synaptic plasticity. Emerging evidence indicates that miRNAs are actively involved in the regulation of synaptic plasticity. Recently, we showed that Wnt-5a is able to control the expression of several miRNAs including miR-101b, which has been extensively studied in carcinogenesis. However, its role in brain is just beginning to be explored...
2015: Frontiers in Cellular Neuroscience
Celina von Stülpnagel, Claudia Funke, Caroline Haberl, Konstanze Hörtnagel, Jerome Jüngling, Yvonne G Weber, Martin Staudt, Gerhard Kluger
BACKGROUND: SYNGAP1, which encodes a RAS-GTPase-activating protein, is located on the short arm of chromosome 6. Heterozygous SYNGAP1 gene mutations have been associated with autism spectrum disorders, delay of psychomotor development, acquired microcephaly, and several forms of idiopathic generalized epilepsy. Here, we report a patient with a new SYNGAP1 stop mutation, and compare the phenotype with published cases with SYNGAP1 mutations and epilepsy. PATIENT: This 15-year-old nondysmorphic girl with intellectual disability developed drop attacks at the age of 2 years, later clonic and clonic-tonic as well as myoclonic seizures predominantly during sleep...
August 2015: Neuropediatrics
Michael J Parker, Alan E Fryer, Deborah J Shears, Katherine L Lachlan, Shane A McKee, Alex C Magee, Shehla Mohammed, Pradeep C Vasudevan, Soo-Mi Park, Valérie Benoit, Damien Lederer, Isabelle Maystadt, Ddd Study, David R FitzPatrick
De novo mutations (DNM) in SYNGAP1, encoding Ras/Rap GTPase-activating protein SynGAP, have been reported in individuals with nonsyndromic intellectual disability (ID). We identified 10 previously unreported individuals with SYNGAP1 DNM; seven via the Deciphering Developmental Disorders (DDD) Study, one through clinical analysis for copy number variation and the remaining two (monozygotic twins) via a research multi-gene panel analysis. Seven of the nine heterozygous mutations are likely to result in loss-of-function (3 nonsense; 3 frameshift; 1 whole gene deletion)...
October 2015: American Journal of Medical Genetics. Part A
Robert A Kozol, Holly N Cukier, Bing Zou, Vera Mayo, Silvia De Rubeis, Guiqing Cai, Anthony J Griswold, Patrice L Whitehead, Jonathan L Haines, John R Gilbert, Michael L Cuccaro, Eden R Martin, James D Baker, Joseph D Buxbaum, Margaret A Pericak-Vance, Julia E Dallman
Despite significant progress in the genetics of autism spectrum disorder (ASD), how genetic mutations translate to the behavioral changes characteristic of ASD remains largely unknown. ASD affects 1-2% of children and adults, and is characterized by deficits in verbal and non-verbal communication, and social interactions, as well as the presence of repetitive behaviors and/or stereotyped interests. ASD is clinically and etiologically heterogeneous, with a strong genetic component. Here, we present functional data from syngap1 and shank3 zebrafish loss-of-function models of ASD...
July 15, 2015: Human Molecular Genetics
Ca Tan, S Topper, D Del Gaudio, V Nelakuditi, O Shchelochkov, Mjm Nowaczyk, S Zeesman, L Brady, L Russell, N Meeks, S Sastry, K Arndt, F Kobiernicki, R Shaw, S Das
Genetic testing for non-specific intellectual disability (ID) presents challenges in daily clinical practice. Historically the focus of the genetic elucidation of non-specific ID has been on genes on the X-chromosome and recent research has brought attention to the growing contribution of autosomal genes. In addition, next generation sequencing (NGS) has greatly improved the ability to simultaneously analyze multiple genetic loci, making large panel testing a practical approach to testing for non-specific ID...
February 19, 2015: Clinical Genetics
Massimiliano Aceti, Thomas K Creson, Thomas Vaissiere, Camilo Rojas, Wen-Chin Huang, Ya-Xian Wang, Ronald S Petralia, Damon T Page, Courtney A Miller, Gavin Rumbaugh
BACKGROUND: Genetic haploinsufficiency of SYNGAP1/Syngap1 commonly occurs in developmental brain disorders, such as intellectual disability, epilepsy, schizophrenia, and autism spectrum disorder. Thus, studying mouse models of Syngap1 haploinsufficiency may uncover pathologic developmental processes common among distinct brain disorders. METHODS: A Syngap1 haploinsufficiency model was used to explore the relationship between critical period dendritic spine abnormalities, cortical circuit assembly, and the window for genetic rescue to understand how damaging mutations disrupt key substrates of mouse brain development...
May 1, 2015: Biological Psychiatry
B J O'Roak, H A Stessman, E A Boyle, K T Witherspoon, B Martin, C Lee, L Vives, C Baker, J B Hiatt, D A Nickerson, R Bernier, J Shendure, E E Eichler
Autism spectrum disorder (ASD) has a strong but complex genetic component. Here we report on the resequencing of 64 candidate neurodevelopmental disorder risk genes in 5,979 individuals: 3,486 probands and 2,493 unaffected siblings. We find a strong burden of de novo point mutations for these genes and specifically implicate nine genes. These include CHD2 and SYNGAP1, genes previously reported in related disorders, and novel genes TRIP12 and PAX5. We also show that mutation carriers generally have lower IQs and enrichment for seizures...
November 24, 2014: Nature Communications
Claire Redin, Bénédicte Gérard, Julia Lauer, Yvan Herenger, Jean Muller, Angélique Quartier, Alice Masurel-Paulet, Marjolaine Willems, Gaétan Lesca, Salima El-Chehadeh, Stéphanie Le Gras, Serge Vicaire, Muriel Philipps, Michaël Dumas, Véronique Geoffroy, Claire Feger, Nicolas Haumesser, Yves Alembik, Magalie Barth, Dominique Bonneau, Estelle Colin, Hélène Dollfus, Bérénice Doray, Marie-Ange Delrue, Valérie Drouin-Garraud, Elisabeth Flori, Mélanie Fradin, Christine Francannet, Alice Goldenberg, Serge Lumbroso, Michèle Mathieu-Dramard, Dominique Martin-Coignard, Didier Lacombe, Gilles Morin, Anne Polge, Sylvie Sukno, Christel Thauvin-Robinet, Julien Thevenon, Martine Doco-Fenzy, David Genevieve, Pierre Sarda, Patrick Edery, Bertrand Isidor, Bernard Jost, Laurence Olivier-Faivre, Jean-Louis Mandel, Amélie Piton
BACKGROUND: Intellectual disability (ID) is characterised by an extreme genetic heterogeneity. Several hundred genes have been associated to monogenic forms of ID, considerably complicating molecular diagnostics. Trio-exome sequencing was recently proposed as a diagnostic approach, yet remains costly for a general implementation. METHODS: We report the alternative strategy of targeted high-throughput sequencing of 217 genes in which mutations had been reported in patients with ID or autism as the major clinical concern...
November 2014: Journal of Medical Genetics
D A Dyment, M Tétreault, C L Beaulieu, T Hartley, P Ferreira, J W Chardon, J Marcadier, S L Sawyer, S J Mosca, A M Innes, J S Parboosingh, D E Bulman, J Schwartzentruber, J Majewski, M Tarnopolsky, K M Boycott
Whole-exome sequencing (WES) has transformed our ability to detect mutations causing rare diseases. FORGE (Finding Of Rare disease GEnes) and Care4Rare Canada are nation-wide projects focused on identifying disease genes using WES and translating this technology to patient care. Rare forms of epilepsy are well-suited for WES and we retrospectively selected FORGE and Care4Rare families with clinical descriptions that included childhood-onset epilepsy or seizures not part of a recognizable syndrome or an early-onset encephalopathy where standard-of-care investigations were unrevealing...
July 2015: Clinical Genetics
William Warnica, Daniele Merico, Gregory Costain, Simon E Alfred, John Wei, Christian R Marshall, Stephen W Scherer, Anne S Bassett
BACKGROUND: MicroRNAs (miRNAs) are key regulators of gene expression in the human genome and may contribute to risk for neuropsychiatric disorders. miRNAs play an acknowledged role in the strongest of genetic risk factors for schizophrenia, 22q11.2 deletions. We hypothesized that in schizophrenia there would be an enrichment of other rare copy number variants (CNVs) that overlap miRNAs. METHODS: Using high-resolution genome-wide microarrays and rigorous methods, we compared the miRNA content of rare CNVs in well-characterized cohorts of schizophrenia cases (n = 420) and comparison subjects, excluding 22q11...
January 15, 2015: Biological Psychiatry
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"