8,241 results match your criteria Neurogenetics [Journal]


APOPT1/COA8 assists COX assembly and is oppositely regulated by UPS and ROS.

EMBO Mol Med 2018 Dec 14. Epub 2018 Dec 14.

MRC-Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK

Loss-of-function mutations in , a gene exclusively found in higher eukaryotes, cause a characteristic type of cavitating leukoencephalopathy associated with mitochondrial cytochrome oxidase (COX) deficiency. Although the genetic association of APOPT1 pathogenic variants with isolated COX defects is now clear, the biochemical link between APOPT1 function and COX has remained elusive. We investigated the molecular role of APOPT1 using different approaches. Read More

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December 2018

ADAPTATIONS OF THE MARSUPIAL NEWBORN: BIRTH AS AN EXTREME ENVIRONMENT.

Anat Rec (Hoboken) 2018 Dec 12. Epub 2018 Dec 12.

Laboratory of Neurogenetics of Language, Rockefeller University, New York, NY, 10065.

At birth a mammalian neonate enters an extreme environment compared to the intrauterine environment in which it has grown. This transition may be particularly extreme in marsupials because they are born at an exceedingly altricial state, after an exceptionally short gestation. Their stage of development must be considered embryonic by almost any criteria. Read More

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December 2018
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Clinical implementation of gene panel testing for lysosomal storage diseases.

Mol Genet Genomic Med 2018 Dec 11. Epub 2018 Dec 11.

Paediatric Neurology Unit, Department of Paediatrics, UZ Brussel, Brussels, Belgium.

Background: The diagnostic workup in patients with a clinical suspicion of lysosomal storage diseases (LSD) is often difficult due to the variability in the clinical phenotype. The gold standard for diagnosis of LSDs consists of enzymatic testing. However, due to the sequential nature of this methodology and inconsistent genotype-phenotype correlations of certain LSDs, finding a diagnosis can be challenging. Read More

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December 2018

Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk.

Science 2018 Dec;362(6420)

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10027, USA.

To explore the developmental reorganization of the three-dimensional genome of the brain in the context of neuropsychiatric disease, we monitored chromosomal conformations in differentiating neural progenitor cells. Neuronal and glial differentiation was associated with widespread developmental remodeling of the chromosomal contact map and included interactions anchored in common variant sequences that confer heritable risk for schizophrenia. We describe cell type-specific chromosomal connectomes composed of schizophrenia risk variants and their distal targets, which altogether show enrichment for genes that regulate neuronal connectivity and chromatin remodeling, and evidence for coordinated transcriptional regulation and proteomic interaction of the participating genes. Read More

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December 2018
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Presence of tau astrogliopathy in frontotemporal dementia caused by a novel Grn nonsense (Trp2*) mutation.

Neurobiol Aging 2018 Nov 20. Epub 2018 Nov 20.

Brain Tissue Bank, Fundación CIEN, Instituto de Salud Carlos III, Madrid, Spain.

Frontotemporal lobar degeneration caused by GRN mutations is mainly associated with a TDP-43 type A proteinopathy. We present a family with autosomal dominant frontotemporal lobar degeneration caused by a novel GRN nonsense mutation (c.5G>A: p. Read More

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November 2018

Correction of half the cardiomyocytes fully rescue Friedreich Ataxia mitochondrial cardiomyopathy through cell-autonomous mechanisms.

Hum Mol Genet 2018 Dec 13. Epub 2018 Dec 13.

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Department of Translational Medicine and Neurogenetics, Illkirch, France.

Friedreich Ataxia (FA) is currently an incurable inherited mitochondrial neurodegenerative disease caused by reduced levels of frataxin. Cardiac failure constitutes the main cause of premature death in FA. While AAV-mediated cardiac gene therapy was shown to fully reverse the cardiac and mitochondrial phenotype in mouse models, this was achieved at high dose of vector resulting in the transduction of almost all cardiomyocytes, a dose and biodistribution that is unlikely to be replicated in clinic. Read More

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December 2018

encephalopathy: A distinctive generalized developmental and epileptic encephalopathy.

Neurology 2018 Dec 12. Epub 2018 Dec 12.

From the Epilepsy Research Centre (D.R.M.V., B.J.S., R.B., M.F.B., S.F.B., M.S.H., I.E.S.), Department of Medicine, University of Melbourne, Austin Health, Australia; Departments of Genetics (D.R.M.V., C.M.A.v.R.-A.) and Neurology (D.R.M.V.), University Medical Center Groningen, University of Groningen, the Netherlands; Pediatric Neurology Unit and Laboratories (D.M., M.M.) and Pediatric Neurology (R.G.), Neurogenetics and Neurobiology Unit and Laboratories, A. Meyer Children's Hospital, University of Florence, Italy; Department of Pediatrics and Pediatric Epilepsy Centre (H.X., W.X.W., Y.J.), Peking University First Hospital, Beijing, China; Department of Pediatrics (C.T.M., H.C.M.), Division of Genetic Medicine, University of Washington, Seattle; Population Health and Immunity Division (M.F.B.), Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Medical Biology (M.F.B.), University of Melbourne, Australia; Caulfield (D.W.), Melbourne, Australia; Department of Clinical Genetics (S.M.M.), Academic Medical Centre, Amsterdam, the Netherlands; Department of Clinical Genetics (A.S.B., G.M.S.M., I.M.B.H.v.d.L.), Erasmus University Medical Centre, Rotterdam, the Netherlands; Department of Clinical Genetics (J.M.v.H.), VU University Medical Center, Amsterdam, the Netherlands; Tasmanian Health Service (T.L.W.), Women's and Children's Services, Launceston General Hospital, Tasmania, Australia; TY Nelson Department of Neurology and Neurosurgery (R.I.W.) and Institute of Neuroscience and Muscle Research (R.I.W.), Children's Hospital at Westmead, Sydney, New South Wales, Australia; Department of Neurosciences (S.M.), Lady Cilento Children's Hospital, Brisbane, Australia; Department of Anatomical Pathology (R.M.K.), Austin Hospital, Melbourne, Australia; IRCCS Stella Maris Foundation (F.S., R.G.), Pisa, Italy; Klinikum Oldenburg (G.C.K.), Zentrum für Kinder-und Jugendmedizin, Klinik für Neuropädiatrie u.angeborene Stoffwechselerkrankungen, Germany; Centre of Epilepsy (Y.J.), Beijing Institute for Brain Disorders, China; Department of Paediatrics (I.E.S.), University of Melbourne, Royal Children's Hospital, Australia; and Florey Institute of Neurosciences and Mental Health (I.E.S.), Australia.

Objective: To delineate the epileptology, a key part of the phenotypic spectrum, in a large patient cohort.

Methods: Patients were recruited via investigators' practices or social media. We included patients with (likely) pathogenic variants or chromosome 6p21. Read More

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December 2018
2 Reads

Adequate evidence to support improved outcomes in depression by primary care physicians compared to psychiatrists when using combinatorial pharmacogenomics.

J Psychiatr Res 2018 Nov 15. Epub 2018 Nov 15.

Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Molecular Brain Science Research Department, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada. Electronic address:

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November 2018

Red Flags for early referral of people with symptoms suggestive of narcolepsy: a report from a national multidisciplinary panel.

Neurol Sci 2018 Dec 12. Epub 2018 Dec 12.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.

Objective: Narcolepsy is a lifelong disease, manifesting with excessive daytime sleepiness and cataplexy, arising between childhood and young adulthood. The diagnosis is typically made after a long delay that burdens the disease severity. The aim of the project, promoted by the "Associazione Italiana Narcolettici e Ipersonni" is to develop Red Flags to detect symptoms for early referral, targeting non-sleep medicine specialists, general practitioners, and pediatricians. Read More

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December 2018

Altered Slc25 family gene expression as markers of mitochondrial dysfunction in brain regions under experimental mixed anxiety/depression-like disorder.

BMC Neurosci 2018 Dec 11;19(1):79. Epub 2018 Dec 11.

Laboratory of Neuropathology Modeling, The Federal Research Center Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia.

Background: Development of anxiety- and depression-like states under chronic social defeat stress in mice has been shown by many experimental studies. In this article, the differentially expressed Slc25* family genes encoding mitochondrial carrier proteins were analyzed in the brain of depressive (defeated) mice versus aggressive mice winning in everyday social confrontations. The collected samples of brain regions were sequenced at JSC Genoanalytica ( http://genoanalytica. Read More

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December 2018

STING-dependent sensing of self-DNA drives silica-induced lung inflammation.

Nat Commun 2018 12 6;9(1):5226. Epub 2018 Dec 6.

CNRS, UMR7355, Orleans, 45071, France.

Silica particles induce lung inflammation and fibrosis. Here we show that stimulator of interferon genes (STING) is essential for silica-induced lung inflammation. In mice, silica induces lung cell death and self-dsDNA release in the bronchoalveolar space that activates STING pathway. Read More

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December 2018
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Utility and implications of exome sequencing in early-onset Parkinson's disease.

Mov Disord 2018 Dec 10. Epub 2018 Dec 10.

Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.

Background: Although the genetic load is high in early-onset Parkinson's disease, thorough investigation of the genetic diagnostic yield has yet to be established. The objectives of this study were to assess variants in known genes for PD and other movement disorders and to find new candidates in 50 patients with early-onset PD.

Methods: We searched for variants either within genes listed by the International Parkinson and Movement Disorder Society Task Force on Genetic Nomenclature or rare homozygous variants in novel candidate genes. Read More

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December 2018
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Bismuth Ferrite Second Harmonic Nanoparticles for Pulmonary Macrophage Tracking.

Small 2018 Dec 10:e1803776. Epub 2018 Dec 10.

Translational Molecular Imaging, Max-Planck Institute for Experimental Medicine, Hermann-Rein-Str. 3, 37075, Göttingen, Germany.

Recently, second harmonic generation (SHG) nanomaterials have been generated that are efficiently employed in the classical (NIR) and extended (NIR-II) near infrared windows using a multiphoton microscope. The aim was to test bismuth ferrite harmonic nanoparticles (BFO-HNPs) for their ability to monitor pulmonary macrophages in mice. BFO-loaded MH-S macrophages are given intratracheally to healthy mice or BFO-HNPs are intranasally instilled in mice with allergic airway inflammation and lung sections of up to 100 μM are prepared. Read More

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December 2018
3 Reads

Periodontal Ehlers-Danlos syndrome is associated with leukoencephalopathy.

Neurogenetics 2018 Dec 8. Epub 2018 Dec 8.

Department of Child Neurology and Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

Here, we report brain white matter alterations in individuals clinically and genetically diagnosed with periodontal Ehlers-Danlos syndrome, a rare disease characterized by premature loss of teeth and connective tissue abnormalities. Eight individuals of two families clinically diagnosed with periodontal Ehlers-Danlos syndrome were included in the present study and underwent general physical, dental, and neurological examination. Whole exome sequencing was performed, and all patients included in the study underwent MRI of the brain. Read More

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December 2018
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Neuregulin 1 type III improves peripheral nerve myelination in a mouse model of congenital hypomyelinating neuropathy.

Hum Mol Genet 2018 Dec 10. Epub 2018 Dec 10.

Hunter James Kelly Research Institute.

Myelin sheath thickness is precisely regulated and essential for rapid propagation of action potentials along myelinated axons. In the peripheral nervous system, extrinsic signals from the axonal protein neuregulin 1 type III regulate Schwann cell fate and myelination. Here we ask if modulating neuregulin 1 type III levels in neurons would restore myelination in a model of congenital hypomyelinating neuropathy (CHN). Read More

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December 2018

Evidence that ITGB3 promoter variants increase serotonin blood levels by regulating platelet serotonin transporter trafficking.

Hum Mol Genet 2018 Dec 7. Epub 2018 Dec 7.

Interdepartmental Program "Autism 0-90", "Gaetano Martino" University Hospital, University of Messina, Italy.

Elevated serotonin (5-HT) blood levels, the first biomarker identified in autism research, has been consistently found in 20-30% of patients with Autism Spectrum Disorder (ASD). Hyperserotonemia is mainly due to greater 5-HT uptake into platelets, mediated by the 5-HT transporter (SERT) located at the platelet plasma membrane. The protein complex involved in platelet SERT trafficking and externalization includes integrin β3, the beta subunit of the platelet membrane adhesive GP IIb/IIIa. Read More

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December 2018

TPP2 mutation associated with sterile brain inflammation mimicking MS.

Neurol Genet 2018 Dec 13;4(6):e285. Epub 2018 Nov 13.

Department of Neurology (E.M.R., S.P., C.S., F.L., F.Z., A.Z.), Medical University of Vienna, Austria; Institut für Humangenetik (E.G., T.W., T.S.), Helmholtz Zentrum München, Germany; Center for Brain Research (T.Z., H.L.), Medical University of Vienna; Division of Nephrology and Dialysis (C.K.), Department of Internal Medicine III, Medical University of Vienna; Department of Physical Medicine (M.K.), Rehabilitation and Occupational Medicine, Medical University of Vienna, Austria; Lübeck Interdisciplinary Platform for Genome Analytics (C.M.L.), Institutes of Neurogenetics and for Cardiogenetics, University of Lübeck; Department of Neurology and Neuroimaging Center (NIC) (C.M.L.), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz; Department of Human Genetics (S.H., J.T.E.), Ruhr-University Bochum; Herdecke (J.T.E.), ZBAF, Faculty of Health, University Witten; Department of Neurology (U.K.Z., M.H.), Neuroimmunological Section, University of Rostock; Department of Neurology (A.D.), Department of Clinical Genomics (A.D.), Department of Neuroscience (A.D.), Jeweils Mayo Clinic, Jacksonville, FL; Department of Neurology (S.G.M.), University of Muenster, Germany; Department of Physiology and Biochemistry (M.A., B.M.), School of Medicine, the University of Jordan; The National Center (Institute) for Diabetes (M.E.-K.), Endocrinology and Genetics (NCDEG), Amman, Jordan; Department of Medical Genetics (C.V.-G., A.D.S.), University of British Columbia, Vancouver, Canada; Department of Medical Biochemistry and Microbiology (B.T.), Uppsala University, Sweden; Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders (W.K.), SMZ-Ost-Donauspital, Vienna, Austria; and Institute for Neuroimmunological and Neurodegenerative Disorders (W.K.), SMZ-Ost-Donauspital, Vienna, Austria.

Objective: To ascertain the genetic cause of a consanguineous family from Syria suffering from a sterile brain inflammation mimicking a mild nonprogressive form of MS.

Methods: We used homozygosity mapping and next-generation sequencing to detect the disease-causing gene in the affected siblings. In addition, we performed RNA and protein expression studies, enzymatic activity assays, immunohistochemistry, and targeted sequencing of further MS cases from Austria, Germany, Canada and Jordan. Read More

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December 2018
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Complexity of the Genetics and Clinical Presentation of Spinocerebellar Ataxia 17.

Front Cell Neurosci 2018 23;12:429. Epub 2018 Nov 23.

Ataxia Centre, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, United Kingdom.

Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the TATA-box binding protein gene (). The disease has a varied age at onset and clinical presentation. It is distinct from other SCAs for its association with dementia, psychiatric symptoms, and some patients presenting with chorea. Read More

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November 2018

Enzymatic and non-enzymatic pathways of kynurenines' dimerization: the molecular factors for oxidative stress development.

PLoS Comput Biol 2018 Dec 10;14(12):e1006672. Epub 2018 Dec 10.

Laboratory of Neurogenetics, Pavlov Institute of Physiology, Russian Academy of Sciences, Saint-Petersburg, Russia.

Kynurenines, the products of tryptophan oxidative degradation, are involved in multiple neuropathologies, such as Huntington's chorea, Parkinson's disease, senile dementia, etc. The major cause for hydroxykynurenines's neurotoxicity is the oxidative stress induced by the reactive oxygen species (ROS), the by-products of L-3-hydroxykynurenine (L-3HOK) and 3-hydroxyanthranilic acid (3HAA) oxidative self-dimerization. 2-aminophenol (2AP), a structural precursor of L-3HOK and 3HAA, undergoes the oxidative conjugation to form 2-aminophenoxazinone. Read More

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December 2018
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Genetic analysis of neurodegenerative diseases in a pathology cohort.

Neurobiol Aging 2018 Nov 17. Epub 2018 Nov 17.

Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Molecular genetic research provides unprecedented opportunities to examine genotype-phenotype correlations underlying complex syndromes. To investigate pathogenic mutations and genotype-phenotype relationships in diverse neurodegenerative conditions, we performed a rare variant analysis of damaging mutations in autopsy-confirmed neurodegenerative cases from the Johns Hopkins Brain Resource Center (n = 1243 patients). We used NeuroChip genotyping and C9orf72 hexanucleotide repeat analysis to rapidly screen our cohort for disease-causing mutations. Read More

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November 2018

Parrot Genomes and the Evolution of Heightened Longevity and Cognition.

Curr Biol 2018 Nov 28. Epub 2018 Nov 28.

Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address:

Parrots are one of the most distinct and intriguing groups of birds, with highly expanded brains [1], highly developed cognitive [2] and vocal communication [3] skills, and a long lifespan compared to other similar-sized birds [4]. Yet the genetic basis of these traits remains largely unidentified. To address this question, we have generated a high-coverage, annotated assembly of the genome of the blue-fronted Amazon (Amazona aestiva) and carried out extensive comparative analyses with 30 other avian species, including 4 additional parrots. Read More

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November 2018

Non-Canonical Control of Neuronal Energy Status by the Na Pump.

Cell Metab 2018 Nov 27. Epub 2018 Nov 27.

Centro de Estudios Científicos (CECs), Casilla 1469, 5110466 Valdivia, Chile. Electronic address:

Neurons have limited intracellular energy stores but experience acute and unpredictable increases in energy demand. To better understand how these cells repeatedly transit from a resting to active state without undergoing metabolic stress, we monitored their early metabolic response to neurotransmission using ion-sensitive probes and FRET sensors in vitro and in vivo. A short theta burst triggered immediate Na entry, followed by a delayed stimulation of the Na/K ATPase pump. Read More

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November 2018

Aberrant Inclusion of a Poison Exon Causes Dravet Syndrome and Related SCN1A-Associated Genetic Epilepsies.

Am J Hum Genet 2018 Dec;103(6):1022-1029

Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA. Electronic address:

Developmental and epileptic encephalopathies (DEEs) are a group of severe epilepsies characterized by refractory seizures and developmental impairment. Sequencing approaches have identified causal genetic variants in only about 50% of individuals with DEEs. This suggests that unknown genetic etiologies exist, potentially in the ∼98% of human genomes not covered by exome sequencing (ES). Read More

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December 2018
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Palliative Care: Perceptions, Experiences, and Attitudes in a Peruvian Neurologic Hospital.

J Palliat Med 2018 Dec 8. Epub 2018 Dec 8.

6 Department of Neurology, University of Washington , Seattle, Washington.

Background: The development of palliative care in Peru remains limited, particularly for nononcological services, such as neurology. The goal of this study was to explore attitudes toward and knowledge about palliative and end-of-life care among patients, families, nurses, and doctors in a specialized neurological institute in Lima, Peru.

Materials And Methods: We used a mixed methods approach consisting of 78 surveys and 21 qualitative, semistructured interviews that were recorded, transcribed, and analyzed using thematic analysis. Read More

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December 2018

P300/CBP-associated factor regulates transcription and function of isocitrate dehydrogenase 2 during muscle differentiation.

FASEB J 2018 Dec 10:fj201800788R. Epub 2018 Dec 10.

Laboratorio di Epigenetica, Istituti Clinici Scientifici Maugeri, Pavia, Italy.

The epigenetic enzyme p300/CBP-associated factor (PCAF) belongs to the GCN5-related N-acetyltransferase (GNAT) family together with GCN5. Although its transcriptional and post-translational function is well characterized, little is known about its properties as regulator of cell metabolism. Here, we report the mitochondrial localization of PCAF conferred by an 85 aa mitochondrial targeting sequence (MTS) at the N terminus region of the protein. Read More

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December 2018

BDNF rs6265 (Val66Met) Polymorphism as a Risk Factor for Blepharospasm.

Neuromolecular Med 2018 Dec 5. Epub 2018 Dec 5.

Laboratory of Neurogenetics, Department of Neurology, University Hospital of Larissa, University of Thessaly, Biopolis, Mezourlo Hill, 41100, Larissa, Greece.

A few genetic variants are implicated in the development of blepharospasm (BSP). The precise role of the rs6265 on the brain-derived neurotrophic factor (BDNF) gene on BSP remains controversial. The effect of rs6265 on BSP was evaluated. Read More

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December 2018
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Association of Pallidal Neurostimulation and Outcome Predictors With X-linked Dystonia Parkinsonism.

JAMA Neurol 2018 Dec 3. Epub 2018 Dec 3.

Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.

Importance: Anecdotal evidence suggests that deep brain stimulation (DBS) of the internal globus pallidus (GPi) is effective in ameliorating dystonia in X-linked dystonia parkinsonism (XDP), a disease that is usually refractive to medical therapy.

Objective: To determine the efficacy of GPi-DBS in a cohort of patients with XDP in a prospective study and identify predictors of postoperative outcomes.

Design, Setting, And Participants: This observational prospective cohort study enrolled patients in February 2013 and was completed in December 2014. Read More

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December 2018
1 Read

LRP10 in α-synucleinopathies.

Lancet Neurol 2018 Dec 13;17(12):1032. Epub 2018 Nov 13.

Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. Electronic address:

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December 2018

FRET-based imaging of intracellular ATP in organotypic brain slices.

J Neurosci Res 2018 Dec 1. Epub 2018 Dec 1.

Faculty of Mathematics and Natural Sciences, Institute of Neurobiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

Active neurons require a substantial amount of adenosine triphosphate (ATP) to re-establish ion gradients degraded by ion flux across their plasma membranes. Despite this fact, neurons, in contrast to astrocytes, do not contain any significant stores of energy substrates. Recent work has provided evidence for a neuro-metabolic coupling between both cell types, in which increased glycolysis and lactate production in astrocytes support neuronal metabolism. Read More

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December 2018
1 Read

Correction: Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.

Mucosal Immunol 2018 Nov 30. Epub 2018 Nov 30.

Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), CNRS and University of Orleans (UMR7355), Orléans, France.

The original version of this Article omitted the author Dr Mathias Chamaillard from the l'Institut de Pasteur, Lille, France. This has been corrected in both the PDF and HTML versions of the Article. Read More

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November 2018
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Single-Cell Sequencing of iPSC-Dopamine Neurons Reconstructs Disease Progression and Identifies HDAC4 as a Regulator of Parkinson Cell Phenotypes.

Cell Stem Cell 2018 Nov 20. Epub 2018 Nov 20.

Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK. Electronic address:

Induced pluripotent stem cell (iPSC)-derived dopamine neurons provide an opportunity to model Parkinson's disease (PD), but neuronal cultures are confounded by asynchronous and heterogeneous appearance of disease phenotypes in vitro. Using high-resolution, single-cell transcriptomic analyses of iPSC-derived dopamine neurons carrying the GBA-N370S PD risk variant, we identified a progressive axis of gene expression variation leading to endoplasmic reticulum stress. Pseudotime analysis of genes differentially expressed (DE) along this axis identified the transcriptional repressor histone deacetylase 4 (HDAC4) as an upstream regulator of disease progression. Read More

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November 2018
1 Read

ANO10 mutational screening in recessive ataxia: genetic findings and refinement of the clinical phenotype.

J Neurol 2018 Dec 4. Epub 2018 Dec 4.

Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20133, Milan, Italy.

Autosomal recessive cerebellar ataxia type 3 (ARCA3) is a rare inherited disorder caused by mutations in the ANO10 gene. The disease is characterized by slowly progressive spastic ataxia variably associated with motor neuron involvement, epilepsy, and cognitive decline. We performed mutational screening in 80 patients with sporadic or autosomal recessive adult-onset ataxia. Read More

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December 2018
2 Reads

Emotion Regulation and the Experience of Future Negative Mood: The Importance of Assessing Social Support.

Front Psychol 2018 20;9:2287. Epub 2018 Nov 20.

Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, United States.

Emotion regulation refers to the use of various strategies, such as cognitive reappraisal and expressive suppression, to help manage our negative experiences, emotions, and thoughts. Although such emotion regulation often occurs within broader social dynamics and interactions, little is known about how social contexts interact with specific regulation strategies to shape the experience of negative emotions. Using data from 544 young adult university students, we provide initial evidence that habitual use of cognitive reappraisal is associated with lower future experience of depression and anxiety primarily through higher perceived social support (PSS). Read More

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November 2018
1 Read

Neurons selectively targeted in frontotemporal dementia reveal early stage TDP-43 pathobiology.

Acta Neuropathol 2018 Dec 3. Epub 2018 Dec 3.

Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.

TAR DNA-binding protein 43 (TDP-43) aggregation is the most common pathological hallmark in frontotemporal dementia (FTD) and characterizes nearly all patients with motor neuron disease (MND). The earliest stages of TDP-43 pathobiology are not well-characterized, and whether neurodegeneration results from TDP-43 loss-of-function or aggregation remains unclear. In the behavioral variant of FTD (bvFTD), patients undergo selective dropout of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices. Read More

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December 2018
2 Reads

Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia.

Nat Med 2018 Dec 3. Epub 2018 Dec 3.

Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Identifying the mechanisms through which genetic risk causes dementia is an imperative for new therapeutic development. Here, we apply a multistage, systems biology approach to elucidate the disease mechanisms in frontotemporal dementia. We identify two gene coexpression modules that are preserved in mice harboring mutations in MAPT, GRN and other dementia mutations on diverse genetic backgrounds. Read More

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December 2018
2 Reads

GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.

Authors:
Nora Franceschini Claudia Giambartolomei Paul S de Vries Chris Finan Joshua C Bis Rachael P Huntley Ruth C Lovering Salman M Tajuddin Thomas W Winkler Misa Graff Maryam Kavousi Caroline Dale Albert V Smith Edith Hofer Elisabeth M van Leeuwen Ilja M Nolte Lingyi Lu Markus Scholz Muralidharan Sargurupremraj Niina Pitkänen Oscar Franzén Peter K Joshi Raymond Noordam Riccardo E Marioni Shih-Jen Hwang Solomon K Musani Ulf Schminke Walter Palmas Aaron Isaacs Adolfo Correa Alan B Zonderman Albert Hofman Alexander Teumer Amanda J Cox André G Uitterlinden Andrew Wong Andries J Smit Anne B Newman Annie Britton Arno Ruusalepp Bengt Sennblad Bo Hedblad Bogdan Pasaniuc Brenda W Penninx Carl D Langefeld Christina L Wassel Christophe Tzourio Cristiano Fava Damiano Baldassarre Daniel H O'Leary Daniel Teupser Diana Kuh Elena Tremoli Elmo Mannarino Enzo Grossi Eric Boerwinkle Eric E Schadt Erik Ingelsson Fabrizio Veglia Fernando Rivadeneira Frank Beutner Ganesh Chauhan Gerardo Heiss Harold Snieder Harry Campbell Henry Völzke Hugh S Markus Ian J Deary J Wouter Jukema Jacqueline de Graaf Jacqueline Price Janne Pott Jemma C Hopewell Jingjing Liang Joachim Thiery Jorgen Engmann Karl Gertow Kenneth Rice Kent D Taylor Klodian Dhana Lambertus A L M Kiemeney Lars Lind Laura M Raffield Lenore J Launer Lesca M Holdt Marcus Dörr Martin Dichgans Matthew Traylor Matthias Sitzer Meena Kumari Mika Kivimaki Mike A Nalls Olle Melander Olli Raitakari Oscar H Franco Oscar L Rueda-Ochoa Panos Roussos Peter H Whincup Philippe Amouyel Philippe Giral Pramod Anugu Quenna Wong Rainer Malik Rainer Rauramaa Ralph Burkhardt Rebecca Hardy Reinhold Schmidt Renée de Mutsert Richard W Morris Rona J Strawbridge S Goya Wannamethee Sara Hägg Sonia Shah Stela McLachlan Stella Trompet Sudha Seshadri Sudhir Kurl Susan R Heckbert Susan Ring Tamara B Harris Terho Lehtimäki Tessel E Galesloot Tina Shah Ulf de Faire Vincent Plagnol Wayne D Rosamond Wendy Post Xiaofeng Zhu Xiaoling Zhang Xiuqing Guo Yasaman Saba Abbas Dehghan Adrie Seldenrijk Alanna C Morrison Anders Hamsten Bruce M Psaty Cornelia M van Duijn Deborah A Lawlor Dennis O Mook-Kanamori Donald W Bowden Helena Schmidt James F Wilson James G Wilson Jerome I Rotter Joanna M Wardlaw John Deanfield Julian Halcox Leo-Pekka Lyytikäinen Markus Loeffler Michele K Evans Stéphanie Debette Steve E Humphries Uwe Völker Vilmundur Gudnason Aroon D Hingorani Johan L M Björkegren Juan P Casas Christopher J O'Donnell

Nat Commun 2018 12 3;9(1):5141. Epub 2018 Dec 3.

Intramural Administration Management Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, 20892, USA.

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Read More

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December 2018
4 Reads
10.742 Impact Factor

CGRP in a gene-environment interaction model for depression: effects of antidepressant treatment.

Acta Neuropsychiatr 2018 Dec 4:1-7. Epub 2018 Dec 4.

3Institution of Clinical Neuroscience, Division of Psychiatry,Karolinska Institutet, S-171 77Sweden.

Objective: Genetic and environmental factors interact in the development of major depressive disorder (MDD). While neurobiological correlates have only partially been elucidated, altered levels of calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) in animal models and in the cerebrospinal fluid of depressed patients were reported, suggesting that CGRP may be involved in the pathophysiology and/or be a trait marker of MDD. However, changes in CGRP brain levels resulting from interactions between genetic and environmental risk factors and the response to antidepressant treatment have not been explored. Read More

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December 2018
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A recurrent de-novo ANO3 mutation causes early-onset generalized dystonia.

J Neurol Sci 2018 Nov 22;396:199-201. Epub 2018 Nov 22.

Institute of Neurogenetics, University of Lübeck, Germany. Electronic address:

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November 2018
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A Chromosomal Deletion and New Frameshift Mutation Cause ARSACS in an African-American.

Front Neurol 2018 15;9:956. Epub 2018 Nov 15.

Department of Neurology, Virginia Commonwealth University, Richmond, VA, United States.

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) is a rare, progressive, neurodegenerative disease characterized by ataxia, spasticity and polyneuropathy. First described in the French-Canadian population of Quebec in 1978, ARSACS has since been identified in multiple patients worldwide. In this clinical case report, we describe the evaluation of an 11-years-old African-American male who presented to neuromuscular clinic for assessment of a gait abnormality. Read More

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November 2018
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Peripubertal cannabidiol treatment rescues behavioral and neurochemical abnormalities in the MAM model of schizophrenia.

Neuropharmacology 2018 Nov 26;146:212-221. Epub 2018 Nov 26.

Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania, Catania, Italy; CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic; National Institute of Mental Health, Klecany, Czech Republic. Electronic address:

In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long-lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, respectively. At the molecular level, an increased cannabinoid receptor type-1 (CB1) mRNA and protein expression, which might be due to reduction in DNA methylation at the gene promoter in the prefrontal cortex (PFC), coincided with deficits in the social interaction test and in the novel object recognition test in MAM rats. Both the schizophrenia-like phenotype and altered transcriptional regulation of CB1 receptors were reversed by peripubertal treatment (from PND 19 to PND 39) with the non-psychotropic phytocannabinoid cannabidiol (30 mg/kg/day), or, in part, by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0. Read More

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November 2018
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De novo truncating variants in PHF21A cause intellectual disability and craniofacial anomalies.

Eur J Hum Genet 2018 Nov 28. Epub 2018 Nov 28.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, Japan.

Potocki-Shaffer syndrome (PSS) is a contiguous gene syndrome caused by 11p11.2 deletions. PSS is clinically characterized by intellectual disability, craniofacial anomalies, enlarged parietal foramina, and multiple exostoses. Read More

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November 2018

MAB21L1 loss of function causes a syndromic neurodevelopmental disorder with distinctive erebellar, cular, cranioacial and enital features (COFG syndrome).

J Med Genet 2018 Nov 28. Epub 2018 Nov 28.

Genome Research Division, Human Genetics Department, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Putative nucleotidyltransferase MAB21L1 is a member of an evolutionarily well-conserved family of the male abnormal 21 (MAB21)-like proteins. Little is known about the biochemical function of the protein; however, prior studies have shown essential roles for several aspects of embryonic development including the eye, midbrain, neural tube and reproductive organs.

Objective: A homozygous truncating variant in has recently been described in a male affected by intellectual disability, scrotal agenesis, ophthalmological anomalies, cerebellar hypoplasia and facial dysmorphism. Read More

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November 2018
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Pharmacological Modulation of the Psychiatric Risk Factor FKBP51 Alters Efficiency of Common Antidepressant Drugs.

Front Behav Neurosci 2018 12;12:262. Epub 2018 Nov 12.

Department Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.

Despite a growing body of research over the last few decades, mental disorders, including anxiety disorders or depression, are still one of the most prevalent and hardest to treat health burdens worldwide. Since pharmacological treatment with a single drug is often rather ineffective, approaches such as co-medication with functionally diverse antidepressants (ADs) have been discussed and tried more recently. Besides classical ADs, there is a growing number of candidate targets identified as potential starting points for new treatment methods. Read More

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November 2018

Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders.

Authors:
Raymond K Walters Renato Polimanti Emma C Johnson Jeanette N McClintick Mark J Adams Amy E Adkins Fazil Aliev Silviu-Alin Bacanu Anthony Batzler Sarah Bertelsen Joanna M Biernacka Tim B Bigdeli Li-Shiun Chen Toni-Kim Clarke Yi-Ling Chou Franziska Degenhardt Anna R Docherty Alexis C Edwards Pierre Fontanillas Jerome C Foo Louis Fox Josef Frank Ina Giegling Scott Gordon Laura M Hack Annette M Hartmann Sarah M Hartz Stefanie Heilmann-Heimbach Stefan Herms Colin Hodgkinson Per Hoffmann Jouke Jan Hottenga Martin A Kennedy Mervi Alanne-Kinnunen Bettina Konte Jari Lahti Marius Lahti-Pulkkinen Dongbing Lai Lannie Ligthart Anu Loukola Brion S Maher Hamdi Mbarek Andrew M McIntosh Matthew B McQueen Jacquelyn L Meyers Yuri Milaneschi Teemu Palviainen John F Pearson Roseann E Peterson Samuli Ripatti Euijung Ryu Nancy L Saccone Jessica E Salvatore Sandra Sanchez-Roige Melanie Schwandt Richard Sherva Fabian Streit Jana Strohmaier Nathaniel Thomas Jen-Chyong Wang Bradley T Webb Robbee Wedow Leah Wetherill Amanda G Wills Jason D Boardman Danfeng Chen Doo-Sup Choi William E Copeland Robert C Culverhouse Norbert Dahmen Louisa Degenhardt Benjamin W Domingue Sarah L Elson Mark A Frye Wolfgang Gäbel Caroline Hayward Marcus Ising Margaret Keyes Falk Kiefer John Kramer Samuel Kuperman Susanne Lucae Michael T Lynskey Wolfgang Maier Karl Mann Satu Männistö Bertram Müller-Myhsok Alison D Murray John I Nurnberger Aarno Palotie Ulrich Preuss Katri Räikkönen Maureen D Reynolds Monika Ridinger Norbert Scherbaum Marc A Schuckit Michael Soyka Jens Treutlein Stephanie Witt Norbert Wodarz Peter Zill Daniel E Adkins Joseph M Boden Dorret I Boomsma Laura J Bierut Sandra A Brown Kathleen K Bucholz Sven Cichon E Jane Costello Harriet de Wit Nancy Diazgranados Danielle M Dick Johan G Eriksson Lindsay A Farrer Tatiana M Foroud Nathan A Gillespie Alison M Goate David Goldman Richard A Grucza Dana B Hancock Kathleen Mullan Harris Andrew C Heath Victor Hesselbrock John K Hewitt Christian J Hopfer John Horwood William Iacono Eric O Johnson Jaakko A Kaprio Victor M Karpyak Kenneth S Kendler Henry R Kranzler Kenneth Krauter Paul Lichtenstein Penelope A Lind Matt McGue James MacKillop Pamela A F Madden Hermine H Maes Patrik Magnusson Nicholas G Martin Sarah E Medland Grant W Montgomery Elliot C Nelson Markus M Nöthen Abraham A Palmer Nancy L Pedersen Brenda W J H Penninx Bernice Porjesz John P Rice Marcella Rietschel Brien P Riley Richard Rose Dan Rujescu Pei-Hong Shen Judy Silberg Michael C Stallings Ralph E Tarter Michael M Vanyukov Scott Vrieze Tamara L Wall John B Whitfield Hongyu Zhao Benjamin M Neale Joel Gelernter Howard J Edenberg Arpana Agrawal

Nat Neurosci 2018 Dec 26;21(12):1656-1669. Epub 2018 Nov 26.

Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Read More

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December 2018
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Dissection of metabolic reprogramming in polycystic kidney disease reveals coordinated rewiring of bioenergetic pathways.

Commun Biol 2018 16;1:194. Epub 2018 Nov 16.

1Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Via Olgettina, 60, Milan, 20132 Italy.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder caused by loss-of-function mutations in or . Increased glycolysis is a prominent feature of the disease, but how it impacts on other metabolic pathways is unknown. Here, we present an analysis of mouse mutant cells and kidneys to investigate the metabolic reprogramming of this pathology. Read More

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November 2018
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Acknowledgement to referees 2017/2018.

Authors:

Neurogenetics 2018 Dec;19(4):263-264

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December 2018

Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder.

Nat Genet 2018 Nov 26. Epub 2018 Nov 26.

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. Read More

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November 2018
13 Reads