Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease, Seventh Edition

Volume 2

7th Edition, Volume 2 - September 27, 2024
Imprint: Academic Press
Editors: Roger N. Rosenberg, Juan M. Pascual
Language: English
Hardback ISBN:
9 7 8 - 0 - 4 4 3 - 1 9 1 7 6 - 3
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 1 9 1 7 7 - 0

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

Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease, Seventh Edition

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Rosenberg’s Molecular and Genetic Basis of Neurologic and Psychiatric Disease, Seventh Edition provides a comprehensive introduction and reference to the foundations and practical aspects relevant to the majority of neurologic and psychiatric disease. This updated volume focuses on degenerative disorders, movement disorders, neuro-oncology, neurocutaneous disorders, epilepsy, white matter diseases, neuropathies and neuronopathies, muscle and neuromuscular junction disorders, stroke, psychiatric disease, and a neurologic gene map. This volume includes new chapters on Von Hippel-Lindau disease, antisocial and violent behavior and Autism. A favorite of over four generations of students, clinicians and scholars, this new edition retains and expands on the informative, concise and critical tone of the previous edition. This is an essential reference for general medical practitioners, neurologists, psychiatrists, geneticists, related professionals, and for the neuroscience and neurology research community at large.

Title of Book
Cover image
Title page
Table of Contents
Copyright
The editors
Dedication
List of Contributors
About the editors
Foreword for the sixth edition
Prologue for the sixth edition
Introduction to the seventh edition
Section I: Degenerative disorders
Chapter 1. Genomics of Alzheimer’s disease
Abstract
Introduction
Single causal genes: amyloid precursor protein, presenilin 1, and presenilin 2
Multiple Alzheimer’s disease risk genes and their interactions with ApoE and Aβ
Interaction of Alzheimer’s disease risk genes and vascular function
ApoE, a single genetic determinant influencing immunotherapy eligibility
Active DNA Aβ42 immunotherapy
Acknowledgments
References
Chapter 2. Parkinson's disease and related disorders
Abstract
Parkinson's disease
Classical Parkinson's disease monogenic genes
Susceptibility loci
Early-onset monogenic Parkinson's disease genes
Atypical parkinsonism monogenic genes
Additional non-PARK monogenic causes of parkinsonism
Atypical parkinsonsim syndromes
Conclusion
Relevant websites
References
Chapter 3. Frontotemporal dementia
Abstract
Terminology
History
Epidemiology
Salience network and frontotemporal dementia
Clinical syndromes
Diagnostic criteria
Histopathology
Genetics of frontotemporal dementia
Treatment in frontotemporal dementia
Conclusions
References
Chapter 4. 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
Acknowledgments
References
Section II: Movement disorders
Chapter 5. The inherited ataxias
Abstract
Introduction
Autosomal dominant ataxias
Other recessive ataxias
Mitochondrial ataxias
Molecular genetics
Therapeutic strategies in genetic ataxias
References
Further reading
Chapter 6. Friedreich ataxia
Abstract
Clinical features
Pathology
Clinical and molecular genetics
Animal and cellular models
Pathogenesis of Friedreich ataxia
Therapy
Clinical management
References
Chapter 7. Clinical and molecular findings in Ataxia–Telangiectasia
Abstract
The clinical features of ataxia-telangiectasia
The molecular functions of ATM and neuropathological consequences of ATM loss
In vitro human model systems of ataxia-telangiectasia neurodegeneration
Treatment and prognosis
References
Chapter 8. Dystonia
Abstract
Clinical features
Molecular genetics and disease mechanisms
Genotype–phenotype correlations
Pleiotropy
Susceptibility genes
Differential diagnosis
Diagnostic testing
Management
Acknowledgment
References
Chapter 9. Huntington’s disease
Abstract
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
References
Chapter 10. The hereditary spastic paraplegias
Abstract
Introduction
Genetic and syndromic classifications
Symptoms, signs, and course of uncomplicated hereditary spastic paraplegia
Gait analysis in hereditary spastic paraplegia
Hereditary spastic paraplegia diagnosis
Apparently sporadic spastic paraplegia versus hereditary spastic paraplegia
Complicated hereditary spastic paraplegia
Clinical variability and genotype–phenotype correlation
Hereditary spastic paraplegia clinical syndromes: six common patterns
Genetic pleiotropy and the occurrence of hereditary spastic paraplegia gene mutations in nonhereditary spastic paraplegia disorders
Emerging gene therapy for hereditary spastic paraplegia
Prognosis
Neuropathology
Molecular basis of hereditary spastic paraplegia
Conclusions
Acknowledgment
References
Section III: Neuro-Oncology
Chapter 11. Glioblastoma
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanisms
Testing
Management
References
Section IV: Neurocutaneous disorders
Chapter 12. Neurofibromatosis type 1
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
Health disparities in neurofibromatosis type 1
Summary
References
Chapter 13. Tuberous sclerosis complex
Abstract
Introduction
Diagnostic criteria
Clinical manifestations
Neurological manifestations
Cardiovascular complications
Renal involvement
Pulmonary complications
Genetic and molecular basis
Genetic counseling
References
Chapter 14. Sturge–Weber syndrome
Abstract
Clinical features
Molecular genetics
Disease mechanisms
Animal models
Differential diagnosis
Testing
Management
Conclusions
Acknowledgments
References
Chapter 15. Hemangioblastomas of the central nervous system
Abstract
Summary
Clinical features
Natural history
Molecular genetics
Disease mechanisms
Diagnostic testing
Management
References
Chapter 16. Incontinentia pigmenti
Abstract
Introduction
Diagnostic criteria
Other minor criteria
Treatment
Perspective
References
Section V: Epilepsy
Chapter 17. Epilepsy genetics in clinical practice today and for the future
Abstract
Introduction
Genetic epidemiology
Monogenic epilepsies
Genetic epilepsy–related comorbidities
Diagnostic testing of genetic epilepsies
Mosaicism in epilepsy
Gene-guided therapies in genetic epilepsies
Summary and future directions
References
Section VI: Lipid metabolism disorders
Chapter 18. Disorders of lipid metabolism
Abstract
Introduction
Pathophysiology
Clinical features
Defects of mitochondrial fatty-acid oxidation
Other disorders of fatty acid β-oxidation
Defects of unsaturated fatty acid oxidation
Acknowledgments
References
Chapter 19. Lipoprotein disorders
Abstract
Introduction
Lipoprotein and lipid metabolism in the central nervous system
Tocopherols
Hypolipidemic disorders involving Apo B proteins
Therapy of hypolipidemic disorders involving Apo B proteins
Disorders of high-density lipoprotein deficiency
Familial lecithin:cholesterol acyltransferase deficiency
Other genetic causes of high-density lipoprotein deficiency
Conclusion
References
Chapter 20. Cerebrotendinous xanthomatosis
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanisms
Diagnosis
Management
References
Section VII: White matter diseases
Chapter 21. Multiple sclerosis
Abstract
Introduction
The clinical features of MS
Diagnosis
Treatment
The biology of MS
Epidemiology and environmental factors
Genetic basis of MS
Neuromyelitis optica
Conclusions
References
Chapter 22. Vanishing white matter
Abstract
Clinical features
Mode of inheritance and prevalence
Natural history
Molecular genetics
Genotype–phenotype correlations
Disease mechanisms
Differential diagnosis
Testing
Management
Therapies under investigation
References
Section VIII: Neuropathies and neuronopathies
Chapter 23. Amyotrophic lateral sclerosis
Abstract
Introduction
Altered conformational stability of critical proteins in ALS
Defects in RNA processing genes and proteins in ALS
Perturbations in aspects of axonal biology in ALS
Other genes
References
Chapter 24. Peripheral neuropathies
Abstract
Introduction
Diverse causes of inherited neuropathies
Myelinating Schwann cells and demyelinating neuropathies
PMP22 deletions cause hereditary neuropathy with liability to pressure palsies
PMP22 duplications cause CMT1A
Other PMP22 pathogenic variants cause DSN, CMT1A, or HNPP
Dominant pathogenic variants in MPZ cause diverse phenotypes
GJB1 pathogenic variants cause CMTX1
Other causes of demyelinating neuropathies
Axons and axonal neuropathies
Hereditary sensory neuropathies
Hereditary motor neuropathies or distal spinal muscular atrophy
The diagnosis and treatment of CMT and related disorders
Transthyretin amyloidosis (ATTR)
Acknowledgments
References
Chapter 25. Spinal muscular atrophy
Abstract
Clinical features
Spinal muscular atrophy Type 1
Spinal muscular atrophy Type 2
Spinal muscular atrophy Type 3
Spinal muscular atrophy Type 4
Proposed classification
Other spinal muscular atrophy variants
Prognosis
Newborn screening
Animal models
Approved gene-modifying therapy: nusinersen
Approved gene-replacement therapy: onasemnogene abeparvovec-xioi (Zolgensma)
Approved gene modifying therapy: risdiplam
Therapies under investigation: myostatin inhibitors, IT onasemnogene, neuromuscular junction augmentation
References
Chapter 26. Pain genetics
Abstract
Introduction
Descending modulation
Hereditary sensory and autonomic neuropathies
Paroxysmal extreme pain disorder
Non-Mendelian human pain genetics
Rodent pain genetics
Future directions
Concluding remarks
References
Section IX: Muscle and neuromuscular junction disorders
Chapter 27. Dystrophinopathies
Abstract
Abbreviations
Clinical characteristics of Duchenne muscular dystrophy/Becker muscular dystrophy
Skeletal myopathy
Central nervous system involvement
Other dystrophinopathy phenotypes
Differential diagnosis
Diagnosis and testing
Molecular genetics
Management
Pharmacotherapy
Supportive care
Therapies under investigation
Targeting muscle health
Targeting gene expression (see Table 27.3)
Acknowledgments
References
Chapter 28. Limb-girdle muscular dystrophy
Abstract
Introduction
Dominant-type limb-girdle muscular dystrophy (LGMD1)
Recessive-type limb-girdle muscular dystrophy (LGMD2)
Differential diagnosis
Managements and future perspectives
References
Chapter 29. The congenital myopathies
Abstract
Summary
Clinical and histopathological features
Molecular genetics and disease mechanisms
Differential diagnosis
Testing
Management
Acknowledgment
References
Chapter 30. The distal myopathies
Abstract
Introduction
Late adult-onset distal myopathies
Distal actininopathy
Early adult-onset distal myopathies
Early onset distal myopathies
Distal myopathy families with very recently identified molecular cause
Conclusion
References
Chapter 31. Hereditary inclusion-body myopathies
Abstract
Introduction
GNE myopathy
Hereditary inclusion-body myopathy with Paget’s 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
References
Chapter 32. The myotonic dystrophies
Abstract
Introduction
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
References
Chapter 33. Facioscapulohumeral muscular dystrophy
Abstract
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
References
Chapter 34. Muscle channelopathies: periodic paralyses and nondystrophic myotonias
Abstract
Introduction
Clinical features
Molecular genetics and disease mechanisms
Differential diagnosis
Testing
Management
References
Chapter 35. Congenital myasthenic syndromes
Abstract
Presynaptic congenital myasthenic syndrome
Defects in acetylcholine receptor
Defects in mechanisms governing endplate development and maintenance
Other myasthenic syndromes
Pharmacotherapy of the congenital myasthenic syndrome
References
Section X: Stroke
Chapter 36. Cerebral vasculopathies
Abstract
Introduction
Genetic disorders affecting vascular structure and integrity
Disorders of vascular occlusion
Disorders of the cerebral small vessels
Approach to identification of genetic vasculopathies
References
Chapter 37. 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
Antithrombin deficiency
Janus kinase-2 (JAK-2 V617F) mutations
Disease mechanisms
Interactions
Management
Summary and future directions
References
Chapter 38. Sickle cell disease
Abstract
Disease characteristics
Hallmark manifestations
Clinical features
Molecular genetics
Disease mechanisms
Testing
Management
Therapies under investigation
Discussion
Acknowledgments
References
Section XI: Metal metabolism disorders
Chapter 39. Wilson disease
Abstract
Introduction
Clinical features
Natural history
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
References
Chapter 40. Menkes disease and other ATP7A disorders
Abstract
Menkes disease
Mouse model of Menkes disease
Occipital horn syndrome
ATP7A-related distal motor neuropathy
Mode of inheritance of ATP7A-related disorders
Acknowledgments
References
Chapter 41. Neurodegeneration with brain iron accumulation
Abstract
Introduction
Natural history
Molecular genetics and genotype–phenotype correlations
Disease mechanisms
Animal models
Investigation
Differential diagnosis
Management
References
Chapter 42. Pantothenate kinase–associated neurodegeneration
Abstract
Introduction
Clinical features
Laboratory findings
Neuroimaging features
Definitive diagnosis
Neuropathological findings
Biological basis of disease
Current treatment strategies
Conclusions and future directions
References
Chapter 43. Disorders of manganese transport
Abstract
Clinical features
Disorders of manganese transport resulting in hypermanganesemia
Disorder of manganese transport resulting in manganese deficiency
Molecular genetics
Disease mechanisms and pathophysiology
Disorders causing hypermanganesemia (HMNDYT1 and HMNDYT2)
Disorder causing hypomanganesemia (CDG2N—SLC39A8 deficiency)
Differential diagnosis
Testing
Management
References
Chapter 44. Aceruloplasminemia
Abstract
Introduction
Classification
Epidemiology
Clinical manifestations
Neuroimaging
Molecular genetics
The role of astrocytes in aceruloplasminemia
Treatment
Short update
References
Section XII: Vitamin disorders
Chapter 45. Genetic and dietary influences on life span
Abstract
Introduction
Hypothesis of longevity and senescence
Caloric intake, α-tocopherol, and other dietary factors
Genetics of aging and life span
Known genetic variants and longevity
Genome-wide studies to identify novel genes
Genetics of biomarkers of aging
Recent developments in longevity research
Conclusion
Acknowledgment
References
Chapter 46. Vitamins: cobalamin and folate
Abstract
Cobalamin
Folate
References
Chapter 47. Inherited disorders associated to biotin and its metabolism
Abstract
Introduction
Biotinidase deficiency
Holocarboxylase synthetase deficiency
Biotin-thiamine-responsive basal ganglia disease (thiamine metabolism dysfunction syndrome 2)
References
Chapter 48. Disorders of pyridoxine metabolism
Abstract
Clinical features
Molecular genetics
PNPO, PLPBP, TNSALP, and PDXK
Disease mechanisms
Testing
Management
Acknowledgments
References
Section XIII: Psychiatric disease
Chapter 49. Unipolar depression
Abstract
Introduction
Clinical phenomenology and epidemiology of depression
Genetics
Mechanisms
Predictive variables
Treatment
Financial disclosure
References
Chapter 50. Bipolar disorder
Abstract
Clinical features
Genetic epidemiology and molecular genetics
Disease mechanisms
Animal models
Management
Conclusion
References
Chapter 51. Schizophrenia
Abstract
Summary
Clinical features
Molecular genetics
Disease mechanisms
Differential diagnosis
Testing
Management
References
Chapter 52. Obsessive–compulsive disorder
Abstract
Summary
Clinical features
Etiology
Prevalence, onset, and evolution
Genetic studies
Disease mechanisms: pathophysiology and current research
Differential diagnosis
Testing
Management
Conclusion
References
Chapter 53. Tourette syndrome
Abstract
Summary
Clinical features
Disease mechanisms: genetics
Disease mechanisms: pathophysiology and current research
Differential diagnosis
Testing
Management
Conclusion
References
Chapter 54. Addiction
Abstract
Introduction
Etiology
Pathophysiology
Preclinical approaches to addiction research
Treatment
Conclusions and future directions
References
Section XIV: A neurologic gene map
Chapter 55. A neurologic gene map
Abstract
References
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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