Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease

5th Edition - October 28, 2014
Imprint: Academic Press
Editors: Roger N. Rosenberg, Juan M. Pascual
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 4 1 0 5 2 9 - 4
eBook ISBN:
9 7 8 - 0 - 1 2 - 4 1 0 5 4 9 - 2

Rosenberg’s Molecular and Genetic Basis of Neurologic and Psychiatric Disease, Fifth Edition provides a comprehensive introduction and reference to the foundations and key pract… Read more

Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease

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Rosenberg’s Molecular and Genetic Basis of Neurologic and Psychiatric Disease, Fifth Edition provides a comprehensive introduction and reference to the foundations and key practical aspects relevant to the majority of neurologic and psychiatric disease. A favorite of over three generations of students, clinicians and scholars, this new edition retains and expands the informative, concise and critical tone of the first edition. This is an essential reference for general medical practitioners, neurologists, psychiatrists, geneticists, and related professionals, and for the neuroscience and neurology research community. The content covers all aspects essential to the practice of neurogenetics to inform clinical diagnosis, treatment and genetic counseling. Every chapter has been thoroughly revised or newly commissioned to reflect the latest scientific and medical advances by an international team of leading scientists and clinicians. The contents have been expanded to include disorders for which a genetic basis has been recently identified, together with abundant original illustrations that convey and clarify the key points of the text in an attractive, didactic format.

Previous editions have established this book as the leading tutorial reference on neurogenetics. Researchers will find great value in the coverage of genomics, animal models and diagnostic methods along with a better understanding of the clinical implications. Clinicians will rely on the coverage of the basic science of neurogenetics and the methods for evaluating patients with biochemical abnormalities or gene mutations, including links to genetic testing for specific diseases.

Cover image
Title page
Table of Contents
Copyright
Dedications
Preface to the Fifth Edition
Contributors
I. General Concepts and Tools
Chapter 1: Mendelian, Non-Mendelian, Multigenic Inheritance, and Epigenetics
Abstract
Introduction
Mendelian traits
Repeat expansion disorders
Non-mendelian inheritance
Chromosomal and genomic disorders
Multigenic inheritance
Complex traits
Epigenetics
The human genome: High-throughput technologies
Conclusions
Chapter 2: Genotype–Phenotype Correlations
Abstract
Introduction
Single phenotype: Multiple genes
Single gene: Multiple phenotypes
Neuronal/cellular selective vulnerability
Highly variable systemic phenotypes
Penetrance and age of onset
Conclusion and future directions
Chapter 3: Immunogenetics of Neurological Disease
Abstract
Introduction
Epidemiological evidence for genetic susceptibility
Genetics of MS: Family-based investigations
The role of major histocompatibility complex genes
Other immune-related genes
The environment and immune-related genes
Conclusion
Chapter 4: Pharmacogenomic Approaches to the Treatment of Sporadic Alzheimer Disease using Cholinomimetic Agents
Abstract
Introduction
Genetic risk factors and sporadic alzheimer disease
Genetic risk factors, cholinergic dysfunction, and alzheimer disease
ApoE4 and cholinomimetic drugs in alzheimer disease
Experimental drugs and their relationship to the apoE4 allele
Acetylcholinesterase and butyrylcholinesterase genetic variants in dementia
Acknowledgements
Chapter 5: Application of Mouse Genetics to Human Disease: Generation and Analysis of Mouse Models
Abstract
Introduction
Creating mouse models
Phenotypic analysis of mouse models
Summary
Chapter 6: DNA Sequencing and Other Methods of Exonic and Genomic Analyses
Abstract
DNA sequencing technologies
NGS for elucidating mendelian-trait diseases
NGS for elucidating molecular bases of diseases with mendelian trait
NGS for elucidating molecular bases of complex-trait diseases
NGS for clinical sequencing
Other methods of exonic and genomic analysis
Chapter 7: Association, Cause and Causal Association: Means, Methods and Measures
Abstract
Learning from infectious disease
Causal “guidelines” and observational Vs. experimental designs
The future?
Chapter 8: Gene Therapy for Neurological Disease
Abstract
Introduction and recent progress
Progress in gene therapy for neurodevelopmental and neurodegenerative disease
Chapter 9: Direct Induction of Neural Stem Cells from Somatic Cells
Abstract
Introduction
Direct induction of NSCs from somatic cells
Comparison of direct induction into NSCs
Direct induction of neural stem cell in regenerative medicine
Chapter 10: Neuroimaging in Dementias
Abstract
Introduction
Neuroimaging technologies
Alzheimer disease
Dementia with lewy bodies
Frontotemporal dementia
Imaging vascular disease
Chapter 11: Cognitive Enhancers and Mental Impairment: Emerging Ethical Issues
Abstract
Introduction
Neuroethics in context
Therapy–enhancement: A false dichotomy
Cognitive enhancers
Personal identity and mental impairments
Identity and enhancement-2
Ethical implications for persons with mental impairment
Recommendations
Conclusion
Chapter 12: Genetic Counseling
Abstract
Genetic counseling defined and providers
Which patients could benefit from genetic counseling?
Components of genetic counseling and case preparation
Risk assessment
Counseling and education about the genetic condition
Genetic testing
Insurance considerations and implications
Test interpretation
Ethical issues
Identifying supportive resources for patients
Conclusions
II. Neurologic Diseases
Chapter 13: Cerebral Malformations
Abstract
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
Chapter 14: Global Developmental Delay and Intellectual Disability
Abstract
Clinical features
Diagnosis
Evaluation and testing
Microdeletion syndromes
Monogenetic causes of ID
X-linked ID
Autosomal dominant ID
Autosomal recessive ID
Disease mechanisms
Management
Chapter 15: Down Syndrome
Abstract
Introduction
Hallmarks of down syndrome
Inheritance
Diagnosis and testing
Early intervention/treatment
Prevalence
Disease evolution
Pathophysiology
Conclusions
Acknowledgements
Chapter 16: An Overview of Rett Syndrome
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanisms
Management
Chapter 17: Fragile X-Associated Disorders
Abstract
Introduction
Disease characteristics
Clinical diagnosis
Historical overview
Mode of inheritance and prevalence
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
Acknowledgements
Conflicts
Chapter 18: Autism Spectrum Disorders: Clinical Considerations
Abstract
Introduction
Overview
Clinical features and diagnostic evaluation
Therapeutic approaches
Chapter 19: Metabolic and Genetic Causes of Autism
Abstract
Introduction
Fragile X syndrome (FRX)
Neurocutaneous syndromes
PhenyLketonuria
Angelman syndrome
Rett syndrome
Smith–lemli–opitz syndrome
In utero drug exposure
Second-hit theory
Summary
Chapter 20: Angelman Syndrome
Abstract
Introduction
Clinical features
Natural history
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
Chapter 21: Prion Diseases
Abstract
Introduction
Origins of discovery
Epidemiology
Pathologic features of prion diseases
Genetics of prion diseases
Cellular prion protein biology
Prion biology
Prion-related proteins
Human prion disease subtypes
Diagnostic studies
Treatment
III. Neurometabolic Disorders
Mitochondrial Disorders
Chapter 22: The Mitochondrial Genome
Abstract
Acknowledgements
Mitochondrial origins
Genome organization
Mitochondrial inheritance
Segregation and heteroplasmy
Mitochondrial DNA replication
Transcription
Translation
Importation
Chapter 23: Mitochondrial Disorders Due to Mutations in the Mitochondrial Genome
Abstract
Introduction
Clinical features
Diagnostic evaluation
Pathology
Biochemical findings
Molecular genetic findings
Animal models
Therapy
Conclusion
Acknowledgements
Chapter 24: Mitochondrial Disorders Due to Mutations in the Nuclear Genome
Abstract
Clinical overview and history
Molecular genetics and disease mechanisms
Testing
Management
Chapter 25: Pyruvate Dehydrogenase, Pyruvate Carboxylase, Krebs Cycle and Mitochondrial Transport Disorders
Abstract
Introduction
Pyruvate dehydrogenase deficiency
Pyruvate carboxylase deficiency
Disorders of the krebs cycle
Mitochondrial transporter disorders
Acknowledgements
Lysosomal Disorders
Chapter 26: Gaucher Disease: Neuronopathic Forms
Abstract
Introduction
Clinical features
Molecular genetics
Pathophysiology
Differential diagnosis
Diagnostic testing
Management
Chapter 27: The Niemann–Pick Diseases
Abstract
Introduction
Clinical features and diagnostic evaluation
Radiologic and neurophysiologic studies
Pathology
Biochemical findings
Brain immunochemical findings
Mechanism of disease
Molecular genetics
Animal models
Therapy
Conclusions
Chapter 28: GM2-Gangliosidoses
Abstract
Introduction
Clinical features
Diagnostic confirmation
Molecular genetics
Disease mechanisms
Imaging
Differential diagnosis
Management
Chapter 29: Metachromatic Leukodystrophy and Multiple Sulfatase Deficiency
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
Chapter 30: Krabbe Disease: Globoid Cell Leukodystrophy
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanisms
Current research
Differential diagnosis
Testing
Management
Acknowledgements
Chapter 31: The Mucopolysaccharidoses
Abstract
Introduction
History
Manifestations of the mucopolysaccharidoses
Therapy for the mucopolysaccharidoses
Chapter 32: The Mucolipidoses
Abstract
Introduction
Manifestations of the mucolipidoses
Chapter 33: Disorders of Glycoprotein Degradation: Sialidosis, Fucosidosis, α-Mannosidosis, β-Mannosidosis, and Aspartylglycosaminuria
Abstract
Introduction
Biosynthesis and biodegradation of glycoproteins
Sialidosis
Fucosidosis
α-Mannosidosis
β-Mannosidosis
Aspartylglycosaminuria
Chapter 34: β-Galactosidase Deficiency: GM1 Gangliosidosis, Morquio B Disease, and Galactosialidosis
Abstract
Introduction
GM1 Gangliosidosis and morquio B disease
GM1 Gangliosidosis
Morquio B disease
Galactosialidosis
Animal models
Status and future possibility of therapy
Acknowledgement
Chapter 35: Acid Ceramidase Deficiency: Farber Lipogranulomatosis and Spinal Muscular Atrophy Associated with Progressive Myoclonic Epilepsy
Abstract
Introduction
Clinical picture
Diagnosis
Pathology
Clinical genetics
Molecular genetics
Animal models
Therapy
Conclusion and future directions
Chapter 36: Wolman Disease
Abstract
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Therapeutic interventions
Chapter 37: Lysosomal Membrane Disorders: LAMP-2 Deficiency
Abstract
Introduction
Danon disease
Clinical features
Management
Chapter 38: Fabry Disease: α-Galactosidase A Deficiency
Abstract
Introduction
Clinical features and diagnostic evaluation
Diagnostic evaluation
Pathology
Biochemistry
Molecular genetics
Treatment
Summary
Acknowledgements
Chapter 39: Schindler Disease: Deficient-N-Acetylgalactosaminidase Activity
Abstract
Introduction
Clinical features and diagnostic results
Diagnostic evaluation
Pathology
Biochemistry
Molecular genetics
Relation to other gene loci
Animal model
Therapy
Future research directions
Acknowledgements
Metal Metabolism Disorders
Chapter 40: Wilson Disease
Abstract
Summary
Clinical features
Natural history
Molecular genetics
Disease mechanisms
Testing
Management
Chapter 41: Menkes Disease and Other ATP7A Disorders
Abstract
Introduction
Menkes disease
Occipital horn syndrome
ATP7A-Related distal motor neuropathy
Mode of inheritance of ATP7A-related disorders
Acknowledgements
Chapter 42: Neurodegeneration with Brain Iron Accumulation
Abstract
Introduction and clinical features
Natural history
Molecular genetics and genotype–phenotype correlations
Disease mechanisms
Investigation
Differential diagnosis
Management
Chapter 43: Pantothenate Kinase-Associated Neurodegeneration
Abstract
Introduction
Clinical features
Laboratory findings
Neuroimaging features
Definitive diagnosis
Neuropathologic findings
Current treatment strategies
Biological basis of disease
Animal models
Burgeoning therapies and rationale
Conclusions and future directions
Chapter 44: Disorders of Manganese Transport
Abstract
Introduction
Clinical features
Molecular genetics
Physiology and disease mechanisms
Differential diagnosis
Testing
Management
Chapter 45: Aceruloplasminemia
Abstract
Clinical features
Laboratory testing
Molecular genetics
Disease mechanisms
Differential diagnosis
Management
Vitamin Disorders
Chapter 46: Genetic and Dietary Influences on Lifespan
Abstract
Introduction
Hypothesis of longevity and senescence
Caloric intake, α-tocopherol, and other dietary factors
Genetics of aging and lifespan
Conclusion
Acknowledgements
Chapter 47: Vitamins: Cobalamin and Folate
Abstract
Cobalamin
Folate
Chapter 48: Disorders of Biotin Metabolism
Abstract
Biotin
Holocarboxylase synthetase deficiency
Biotinidase deficiency
Biotin-responsive basal ganglia disease
Conclusion
Chapter 49: Disorders of Pyridoxine Metabolism
Abstract
Introduction
Clinical features
Natural history
Molecular genetics: ATQ
Molecular genetics: PNPO and TNSALP
Disease mechanisms and pathophysiology
Differential diagnosis
Testing
Management
Acknowledgements
Lipid Metabolism Disorders
Chapter 50: Disorders of Lipid Metabolism
Abstract
Introduction
Pathophysiology
Clinical features
Defects of mitochondrial fatty-acid oxidation
Other disorders of fatty-acid β-Oxidation
Acknowledgements
Chapter 51: Lipoprotein Disorders
Abstract
Introduction
Lipoprotein structure and metabolism
Disorders of lipoproteins containing apoprotein B
Disorders of high-density lipoproteins
Conclusion
Addendum
Chapter 52: Cerebrotendinous Xanthomatosis
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanisms
Diagnosis
Management
Other Metabolic Disorders
Chapter 53: Organic Acid Disorders
Abstract
Introduction
Clinical features
Natural history
Pathophysiology
Differential diagnosis
Molecular genetics
Testing
Management
Chapter 54: Glycogen Storage Diseases
Abstract
Introduction
Clinical features
Diagnostic evaluation
Pathology
Biochemical findings
Molecular genetic findings
Animal models
Therapy
Conclusion
Acknowledgement
Chapter 55: Disorders of Galactose Metabolism
Abstract
Introduction
Classic galactosemia
Uridine diphosphate-galactose 4′-Epimerase deficiency
Galactokinase deficiency
Fanconi–bickel syndrome
Portosystemic venous shunting and hepatic arteriovenous malformations
Chapter 56: Inborn Errors of Amino Acid Metabolism
Abstract
Phenylketonuria and disorders of biopterin metabolism
Hepatorenal tyrosinemia
Nonketotic hyperglycinemia
Maple syrup urine disease
Chapter 57: Urea Cycle Disorders
Abstract
Introduction
Clinical features
Natural history
Molecular genetics
Expression of urea cycle enzymes and nitrogen metabolism
Disease mechanisms/pathophysiology
Differential diagnosis
Testing
Management
Current research
Chapter 58: Glucose Transporter Type I Deficiency and Other Glucose Flux Disorders
Abstract
Overview of glucose transport
Clinical features
Molecular genetics of GLUT1 deficiency
Disease mechanisms in GLUT1 deficiency
Animal models of GLUT1 deficiency
Differential diagnosis of GLUT1 deficiency
Testing for GLUT1 deficiency
Management of GLUT1 deficiency
Acknowledgements
Chapter 59: Maple Syrup Urine Disease: Clinical and Therapeutic Considerations
Abstract
Introduction
Clinical presentation of classic MSUD
Neuropathology of MSUD
Variant types of MSUD
Genetics and prevalence
Component enzymes and macromolecular organization of BCKDC
The thiamine-responsive phenotype is linked to the presence of mutant E2 proteins
Animal models for classic and intermediate MSUD
Treatments of MSUD
Concluding remarks
Acknowledgements
Chapter 60: Congenital Disorders of N-linked Glycosylation
Abstract
Introduction
Clinical features and diagnostic evaluation
Pathology
Molecular genetic data
Animal models
Therapy
Conclusion
Chapter 61: Disorders of Glutathione Metabolism
Abstract
Introduction
GSH and the γ-glutamyl cycle
Disorders of enzymes in the γ-glutamyl cycle
Excitatory amino acid transporters (EAATs)
Disorders of EAAC1 leading to GSH depletion
Neurodegenerative diseases leading to GSH depletion
Conclusions
Chapter 62: Canavan Disease
Abstract
Introduction
History
Basic defect
Clinical features
Diagnosis
Differential diagnosis
Epidemiology
Molecular basis
Prevention/prenatal diagnosis
Management
Therapy
Chapter 63: Neurotransmitter Disorders
Abstract
Introduction
Disorders of monoamines
Disorders of gaba
Pyridoxine-responsive epilepsy
Pyridoxamine 5′-phosphate oxidase deficiency
Chapter 64: Peroxisomal Disorders
Abstract
Introduction
Disorders of peroxisome biogenesis
Peroxisomal disorders due to defects in single peroxisomal enzymes
Other peroxisomal single-enzyme defects
Chapter 65: Disorders of Purine Metabolism
Abstract
Lesch–Nyhan Disease
Phosphoribosylpyrophosphate (PRPP) Synthetase Abnormalities
Chapter 66: The Porphyrias
Abstract
Introduction
Porphyria: clinical aspects
Diagnosis
Pathogenesis of neurologic symptoms
Chemical and physiologic inducers of acute porphyria
Molecular genetics
Animal models
Therapy
Prognosis
IV. Degenerative Disorders
Chapter 67: Alzheimer Disease
Abstract
Introduction
Clinical features and diagnosis
Pathology
Biochemical findings
Molecular genetic analysis of alzheimer disease
Therapy
Chapter 68: Genetics of Parkinson Disease and Related Diseases
Abstract
Introduction
Parkinson disease
Parkinson-plus syndromes
Conclusions
Chapter 69: Frontotemporal Dementia
Abstract
History and terminology
Epidemiology
Clinical syndromes
Diagnostic criteria
Histopathology
Genetics
Treatment
Conclusions
Chapter 70: The Neuronal Ceroid-Lipofuscinoses (Batten Disease)
Abstract
Introduction
Historical overview
Mode of inheritance, incidence and prevalence
Natural history
Molecular genetics
Disease mechanisms
Differential diagnosis and testing
Management
Conclusion
Acknowledgements
V. Movement Disorders
Chapter 71: The Inherited Ataxias
Abstract
Introduction
Autosomal dominant ataxias
Autosomal recessive ataxias
Other recessive ataxias
Mitochondrial ataxias
Molecular genetics
Therapeutic strategies in genetic ataxias
Chapter 72: Friedreich Ataxia
Abstract
Clinical features
Pathology
Clinical and molecular genetics
Animal and cellular models
Pathogenesis of friedreich ataxia
Therapy
Chapter 73: Ataxia-Telangiectasia
Abstract
Clinical features
Molecular pathology
Diagnosis and differential diagnosis
Treatment and prognosis
Chapter 74: Dystonia
Abstract
Definition
Classification
Genetic causes
Pleiotropy
Susceptibility genes
Acknowledgement
Chapter 75: Huntington Disease
Abstract
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
Chapter 76: Non-Parkinsonian Movement Disorders
Abstract
Introduction
Essential tremor
Dystonia
Chorea
Myoclonus epilepsy
Paroxysmal dyskinesias
Hereditary hyperekplexia
Tourette syndrome
Fragile X-associated tremor/ataxia syndrome
Movement disorders, genetics, multidisciplinary care, and the future
Chapter 77: Hereditary Spastic Paraplegia
Abstract
Introduction
Genetic and syndromic classifications
Symptoms, signs, and course of uncomplicated HSP
HSP Diagnosis
Complicated HSP
Clinical variability and genotype–phenotype correlation
Treatment
Prognosis
Neuropathology30–37
Molecular basis of HSP
Conclusions
Acknowledgements
VI. Neuro-Oncology
Chapter 78: Glioblastoma
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanisms
Testing
Management
VII. Neurocutaneous Disorders
Chapter 79: Neurofibromatoses
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanism
Differential diagnosis
Genetic testing
Management
Future directions
Chapter 80: Tuberous Sclerosis Complex
Abstract
Introduction
Clinical manifestations
Diagnostic criteria
Genetic and molecular basis
Chapter 81: Sturge–Weber Syndrome
Abstract
Clinical features
Natural history
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
Acknowledgements
Chapter 82: Hemangioblastomas of the Central Nervous System
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanisms
Diagnostic testing
Management
Chapter 83: Incontinentia Pigmenti
Abstract
Introduction
Diagnostic criteria for IP
Skin manifestations of IP
CNS manifestations of IP
Ocular manifestations of IP
Disorders of skin appendages in IP
Bony manifestations of IP
Dental and oral manifestations of IP
Other minor criteria
Genetics of IP
IP in males
Treatment and future directions
VIII. Epilepsy
Chapter 84: The Genetic Epilepsies
Abstract
Introduction
Defining epilepsy genes and genetic epilepsy syndromes
Human genetic epilepsy syndromes
Pathophysiology of selected epilepsy gene mutations
Conclusion
IX. White Matter Diseases
Chapter 85: Multiple Sclerosis
Abstract
Introduction
Clinical features
Diagnosis
Disease-modifying treatment
Pathology
Immunologic basis
Epidemiology
Genetic basis of MS
Conclusions
Chapter 86: Vanishing White Matter Disease
Abstract
Clinical features
Molecular genetics
Disease mechanisms and pathophysiology
Differential diagnosis
Testing
Management
X. Neuropathies and Neuronopathies
Chapter 87: Amyotrophic Lateral Sclerosis
Abstract
Introduction
Altered conformational stability and turnover of critical proteins in ALS
Defects in rna processing genes and proteins in ALS
Candidate als genes implicated in transcriptional regulation
Perturbations in aspects of axonal biology in ALS
Genome-wide association studies (GWAS) in ALS
Chapter 88: Peripheral Neuropathies
Abstract
Introduction
Classifying inherited neuropathies
Diagnosis and treatment of cmt and related disorders
Amyloid neuropathies
Acknowledgements
Chapter 89: Spinal Muscular Atrophy
Abstract
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
Chapter 90: Pain Genetics
Abstract
Introduction
Neurobiology of pain
Mendelian disorders of pain
Non-mendelian pain genetics
Future directions
Concluding remarks
XI. Muscle and Neuromuscular Junction Disorders
Chapter 91: Dystrophinopathies
Abstract
Historical overview
Mode of inheritance and prevalence
Natural history
Disease variants
End of life: Mechanisms and comorbidities
Molecular genetics
Biochemistry
Pathophysiology and animal models
Experimental therapy and future research directions
Chapter 92: Limb-Girdle Muscular Dystrophy
Abstract
Introduction
LGMD1
LGMD2
Animal models
Differential diagnosis
Management and future perspectives
Chapter 93: The Congenital Myopathies
Abstract
Introduction
Clinical and histopathological features
Molecular genetics and disease mechanisms
Differential diagnosis
Testing
Management
Chapter 94: The Distal Myopathies
Abstract
Introduction
Late adult-onset distal myopathies
Early adult-onset distal myopathies
Early-onset distal myopathies
Single distal myopathy families with unknown molecular cause
Conclusion
Chapter 95: Hereditary Inclusion-Body Myopathies
Abstract
Introduction
Gne myopathy
Hereditary inclusion-body myopathy with paget disease of the bone and frontotemporal dementia
Hereditary inclusion-body myopathy with congenital joint contractures and external ophthalmoplegia
Other variants of hereditary inclusion-body myopathy
Chapter 96: The Myotonic Dystrophies
Abstract
Introduction
Clinical features
Natural history
Molecular genetics
Differential diagnosis and testing
Management
Chapter 97: Facioscapulohumeral Dystrophy
Abstract
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
Chapter 98: Muscle Channelopathies: Periodic Paralyses and Nondystrophic Myotonias
Abstract
Introduction
Clinical features
Molecular genetics and disease mechanisms
Differential diagnosis
Testing
Management
Acknowledgement
Chapter 99: Congenital Myasthenic Syndromes
Abstract
Introduction
Presynaptic CMS
Defects in basal lamina proteins
Defects in AChR
Defects in mechanisms governing EP development and maintenance
Defects of glycosylation
Other myasthenic syndromes
Pharmacotherapy of the CMS
XII. Stroke
Chapter 100: Cerebral Vasculopathies
Abstract
Introduction
Inborn errors of metabolism with cerebrovascular involvement
Genetic disorders with early atherosclerosis
Genetic disorders with increased prevalence of dissection
Moyamoya
Genetic causes of small vessel disease
Chapter 101: Coagulopathies
Abstract
Introduction
β-Fibrinogen on chromosome 4q28
Factor ii (prothrombin) gene 20210g > a on 11p11-q12
Factor v leiden
Thermolabile methylene tetrahydrofolate reductase polymorphism
Disease mechanisms
Management
Summary and future directions
Chapter 102: Sickle Cell Disease
Abstract
Introduction
Disease characteristics
Clinical features
Natural history
Molecular genetics
Pathology
Clinical presentation
Disease mechanisms and pathophysiology
Testing
Management
Discussion
Acknowledgements
XIII. Psychiatric Disease
Chapter 103: Depression
Abstract
Introduction
Clinical features
Pathology: Biochemical alterations
Pathology: Functional neurobiology
Pathology: Neural plasticity and resilience
Treatment: Mechanism of antidepressant action
Genetics: Unipolar depression as a heritable disease
Genetic studies: The search for quantitative traits
Epigenetics: Environmental influence at the genetic level
Conclusion: Reducing burden by increasing therapeutic effect
Financial Disclosures
Chapter 104: Bipolar Disorder
Abstract
Introduction
Clinical features
Genetic epidemiology
Disease mechanisms
Molecular genetics
Animal models
Management
Conclusion
Chapter 105: Schizophrenia
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
Chapter 106: Obsessive–Compulsive Disorder
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanisms: pathophysiology and current research
Differential diagnosis
Testing
Management
Conclusion
Chapter 107: Tourette Syndrome
Abstract
Summary
Clinical features
Disease mechanisms: pathophysiology and current research
Differential diagnosis
Testing
Management
Conclusions
Acknowledgements
Chapter 108: Addiction
Abstract
Disease characteristics, clinical features and diagnostic evaluation
Human molecular and genetic data
Behavioral neuroscience frameworks
Genetic animal models
Molecular approaches
Therapy
Conclusions and future directions
Acknowledgements
XIV. A Neurologic Gene Map
Chapter 109: A Neurologic Gene Map
Abstract
Index

Roger N. Rosenberg

Roger N. Rosenberg, MD is a graduate of Northwestern University Medical School, With Distinction, and was subsequently trained in Neurology with H. Houston Merritt, MD at the Neurological Institute, Columbia University, New York, was Chief Resident and then was a Post-Doctoral Fellow with Nobel Laureate Marshall Nirenberg at the NIH in the Laboratory of Biochemical Genetics. He is Board Certified by the American Board of Psychiatry and Neurology. He is holder of the Zale Distinguished Chair and Professor of Neurology and Neurotherapeutics at the University of Texas Southwestern Medical Center at Dallas since 1973 and developed the department for 18 years as Chair from 1973-1991. He described for the first time in 1975 Machado Joseph disease, an autosomal dominant cerebellar degeneration, which produces imbalance and impaired coordination, and showed it was due to a unique expansion of DNA in the causal gene. It is the most common inherited form of impaired coordination in the world and his research has provided a genetic marker to eliminate it in large families in future generations. He has served as the Founding Director of the UT Southwestern NIH funded Alzheimer’s Disease Center and Principal Investigator of the NIH Center Grant from 1987-2019. He directs an active laboratory effort in Alzheimer’s Disease. He is developing a DNA Aβ42 trimer vaccine for Alzheimer's disease for which he was awarded a US Patent "Amyloid Beta Gene Vaccines" in January 2009. It has been tested in mouse, transgenic mouse, New Zealand white rabbits and rhesus monkeys. The vaccine produces effective anti-Aβ42 peptide antibody levels and is non-inflammatory in all three species. The vaccine reduces by 40% Aβ42 peptide and by 50% tau and phospho-tau in the brains of 3X AD Tg mice, the two main pathologies of Alzheimer’s disease, with high levels of anti-Aβ42 antibody and with a non-inflammatory immune response. He is preparing now a Phase 1 Clinical trial Grant - First in Human to determine its effectiveness and safety in human subjects. He has published 297 original scientific articles, chapters, reviews, and editorials. He served as Editor in Chief from 1997 through 2017 for JAMA Neurology (formerly Archives of Neurology), a major international neurology journal, published by the American Medical Association. During his tenure, he raised the Impact Factor of the journal from 3.0 to 10.2, placing JAMA Neurology as #1 of all US publications in neurology. He is the founding editor of two of the landmark texts in neuroscience. Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease, 5th edition, published in 2015 by Elsevier. The 6th edition will publish in 2020. The Atlas of Clinical Neurology, 4th edition, has just been published. He is a former President of the American Academy of Neurology, former Vice-President of the American Neurological Association, an Honorary Member of both organizations, and a Fellow of the American Association for the Advancement of Science. He received the first Science Medal in 2009 from the World Federation of Neurology for his contributions to neuro-genetics, for his original clinical and molecular genetics research on Machado-Joseph disease, and the development of the DNA Abeta42 trimer vaccine for Alzheimer’s disease.

Affiliations and expertise

Abe (Brunky), Morris and William Zale Distinguished Chair in Neurology, Professor of Neurology and Neurotherapeutics, Founding Director, Alzheimer’s Disease Center Head, Section on Memory and Behavioral Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

Juan M. Pascual

Juan M. Pascual, M.D., Ph.D., is the inaugural holder of The Once Upon a Time Foundation Professorship in Pediatric Neurologic Diseases and also holds the Ed and Sue Rose Distinguished Professorship in Neurology. His laboratory research interests span virtually the entire field of neuroscience, including medical neuroscience, from molecular structure and function (including drug action), neural physiology and metabolism at the cellular, circuit and whole-brain level and neurogenetics, all of which is complemented with neurological patient care and clinical trials. Laboratory research greatly influences his clinical activities and patient observations guide his laboratory research direction. As a clinician, Dr. Pascual specializes in genetic and metabolic diseases of the nervous and neuromuscular systems of infants, children, and adults with a particular emphasis on complex diagnostic problems, second opinions for patients visiting from the rest of the U.S. and abroad, and in clinical trials. Dr. Pascual has special clinical research expertise in undiagnosed and rare diseases, glucose metabolism, mitochondrial, degenerative, and multi-organ disorders. Dr. Pascual is a tenured faculty member in four Departments at UT Southwestern Medical Center: Neurology and Neurotherapeutics, Physiology, Pediatrics, and the Eugene McDermott Center for Human Growth & Development / Center for Human Genetics. He is also Director of the Rare Brain Disorders Program (Clinic and Laboratory). He is also a member of the Division of Pediatric Neurology, of the graduate Ph.D. programs in Neuroscience and Integrative Biology, and of the postgraduate clinical training programs in Neurology, Pediatric Neurology, Pediatrics, and Medical Genetics. He teaches at UT Southwestern Medical School. In addition, Dr. Pascual is an adjunct professor in the Department of Biological Sciences at the School of Natural Sciences and Mathematics, The University of Texas at Dallas. Dr. Pascual directs a highly collaborative research laboratory and is credentialed campus-wide at Children's Medical Center Dallas, UT Southwestern University Hospitals and Clinics, and Parkland Memorial Hospital, where he consults on inpatients and outpatients with particularly complex or severe diseases. Much of his research is funded by the National Institutes of Health. Dr. Pascual received his M.D. degree with unique distinction from the Universidad de Granada, Spain, one of the oldest universities in the world, founded in 1349 by Yusuf I, Sultan of Granada and one of the builders of the Alhambra. He received his Ph.D. degree in Molecular Physiology and Biophysics from Baylor College of Medicine in Houston, Texas, under Arthur M. Brown, M.D., Ph.D., McCollum Professor and Chair. His postdoctoral research was conducted under Arthur Karlin, Ph.D., Higgins Professor and Director of the Center for Molecular Recognition, College of Physicians and Surgeons of Columbia University and, later, at the Colleen Giblin Research Laboratories for Pediatric Neurology at the same institution under a Neurological Sciences Academic Development Award from the National Institute of Neurological Disorders and Stroke. He also received residency training in Pediatrics at Washington University School of Medicine - St. Louis Children's Hospital and in Neurology and Pediatric Neurology at the Neurological Institute of New York - Columbia University Medical Center. He received certification in Neurology with Special Qualification in Child Neurology from the American Board of Psychiatry and Neurology.

Affiliations and expertise

Dept Neurology and Neurotherapeutics, Physiology and Pediatrics; McDermott Ctr for Human Growth and Dev/Ctr for Human Genetics, Univ of Texas Southwestern Medical Ctr, Dallas, TX, USA

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