UID:
almahu_9948025763302882
Format:
1 online resource (417 pages) :
,
illustrations.
ISBN:
0-444-63235-2
,
0-444-63233-6
Series Statement:
Handbook of Clinical Neurology ; Volume 147
Note:
Front Cover -- Neurogenetics, Part I -- Copyright -- Handbook of Clinical Neurology 3rd Series -- Foreword -- Preface -- Contributors -- Contents of Part I -- Contents of Part II -- Section I: Basic genetic concepts -- Chapter 1: Clinical approach to the patient with neurogenetic disease -- Factors suggesting a neurogenetic disorder -- Nonspecific categories masking neurogenetic diseases -- Importance of family history -- Assessment of sporadic/simplex cases -- Genetic counseling -- Genetic testing -- Neurogenetics information resources -- An integrated clinical neurogenetics strategy -- Acknowledgment -- References -- Chapter 2: Genetic and genomic testing for neurologic disease in clinical practice -- The contribution of genetics to neurologic disease -- The importance of phenotyping and other clinical considerations -- Methods of single-gene diagnostic testing -- Gene sequencing -- Detection of other forms of gene mutation -- Multigene panel testing -- Methods for genomic diagnostic testing -- Chromosomal microarray analysis -- Whole-exome sequencing -- Strategies for a comprehensive genetic evaluation in heterogeneous phenotypes -- Variants of unknown significance and incidental findings -- Future directions -- Acknowledgments -- References -- Chapter 3: Ethical issues in neurogenetics -- Introduction -- Core ethical principles and concepts -- Decisional capacity -- Informed consent -- Predictive genetic testing -- Guidelines -- Predictive genetic testing considerations -- Testing minor children -- Testing an adult child when at-risk parent has not been tested -- Testing patient's at-risk relatives who have just learned they are at risk -- Testing patients with psychiatric issues -- Testing patients with cognitive impairment -- Prenatal testing for neurogenetic conditions -- Communication/noncommunication of genetic test results.
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When a patient declines results disclosure -- When a patient declines to inform other family members -- Is there a duty to warn? -- Insurance implications and potential for genetic discrimination -- Anonymous testing -- What to do when ethical issues arise -- Consulting with genetics specialists -- Key emerging issues -- Direct-to-consumer genetic testing -- Disclosure of secondary (incidental) findings -- Using genetic testing to determine eligibility for clinical trials -- Use of genetic testing to screen for vulnerability -- Conclusion -- References -- Chapter 4: Evolving views of human genetic variation and its relationship to neurologic and psychiatric disease -- The contribution of common versus rare genetic variation -- Why does the frequency of genetic variation matter? -- Evolving views of genome function -- References -- Chapter 5: Epigenetic mechanisms underlying nervous system diseases -- Introduction -- Epigenetic mechanisms -- DNA methylation -- Cytosine methylation, oxidation, and demethylation -- Distribution and functions of DNA methylation -- Chromatin remodeling -- Histone modifications, nucleosome remodeling/repositioning, and higher-order chromatin reorganization -- Noncoding RNAs -- Short noncoding RNAs -- Long noncoding RNAs -- RNA editing -- Emerging epigenetic mechanisms -- Emerging roles of epigenetic mechanisms in neurobiologic processes -- Emerging roles of epigenetic mechanisms in nervous system diseases -- Mutations in genes encoding epigenetic factors -- Genetic variation in genes encoding epigenetic factors and those targeted by epigenetic factors -- Impairments in epigenetic factor expression, localization, and function -- Epigenetic mechanisms modulating disease-associated factors and pathways -- Aberrant epigenetic profiles and epigenetic epidemiology -- Promise of epigenetic medicine.
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Conclusion and future directions -- Acknowledgments -- References -- Chapter 6: Pharmacogenetics -- Introduction -- Pharmacogenetic influences on pharmacokinetics -- Pharmacogenetic influences on pharmacodynamics -- Hypersensitivity reactions -- Parkinson's disease -- Alzheimer's disease -- Psychiatric disorders -- Antidepressants -- Antipsychotics -- Summary and conclusions -- References -- Chapter 7: Bioinformatics and genomic databases -- Introduction -- DNA -- Genotyping arrays -- Whole-genome and whole-exome sequencing -- Disease genetics -- Epigenetic markers and regulatory features -- Transcription factors -- Histone modifications -- RNA And proteins -- Publicly available gene expression data -- Spatiotemporal patterns of gene expression -- Gene function -- Pathways and gene networks -- Pathways -- Biomedical literature mining -- Protein-protein interactions (PPI) -- Coexpression -- Database collections -- Conclusion and future directions -- References -- Chapter 8: Towards precision medicine -- Introduction -- Recent advances in genetics and precision medicine -- Current state of precision neurology -- Precision diagnostics -- Targeted genetic diagnosis -- Novel diagnostic approaches: the example of whole-exome sequencing -- Expanding precision diagnostics to general practice -- The genetic counselor -- Personalized therapeutics -- Pharmacogenomics -- Identification of nonresponders -- Avoidance of adverse effects -- Dose optimization -- Gene therapy -- CHALLENGES -- Personalized neurology at work -- Conclusion -- References -- Section II: Recurring biological themes in neurogenetics -- Chapter 9: Repeat expansion diseases -- Introduction -- General features -- Genetic testing -- Diverse molecular mechanisms -- The diseases -- Fragile X syndrome, fragile X tremor ataxia syndrome, and other fragile X sites -- Myotonic dystrophy types 1 and 2.
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CAG/polyglutamine diseases -- Other repeat expansion SCAs -- Spinocerebellar ataxia type 8 -- Spinocerebellar ataxia type 10 -- Spinocerebellar ataxia type 12 -- Spinocerebellar ataxia type 31 -- Spinocerebellar ataxia type 36 -- Huntington disease-like 2 (HDL2) -- Friedreich ataxia -- Unverricht-Lundborg myoclonic epilepsy -- Oculopharyngeal muscular dystrophy -- Fuchs endothelial corneal dystrophy (FECD) -- C90RF72 FTD/ALS -- References -- Chapter 10: Mitochondrial diseases -- Introduction -- Historic perspectives -- Mitochondrial function and DNA -- Mitochondrial DNA mutations and human disease -- Nuclear DNA mutations and human disease -- Prevalence -- Approach to diagnosis -- Clinical findings in mitochondrial diseases -- Family history -- Laboratory investigations -- Genetic testing -- Treatment options for mitochondrial disease -- Disease-specific treatments -- Prenatal genetic diagnosis, preimplantation diagnosis, and mitochondrial donation therapy -- Summary -- References -- Chapter 11: The CAG-polyglutamine repeat diseases: a clinical, molecular, genetic, and pathophysiologic nosology -- Introduction -- Spinal and bulbar muscular atrophy -- Huntington disease -- Dentatorubral pallidoluysian atrophy -- Spinocerebellar ataxia type 1 -- Spinocerebellar ataxia type 2 -- Spinocerebellar ataxia type 3 (AKA machado-joseph disease) -- Spinocerebellar ataxia type 6 -- Spinocerebellar ataxia type 7 -- Spinocerebellar ataxia type 17 -- Common themes in polyglutamine disease pathogenesis -- Protein aggregation and cleavage -- Transcription dysregulation - gain of function, loss of function, or both? -- Autophagy impairment -- Mitochondrial dysfunction -- Towards therapy -- Acknowledgments -- References -- Section III: Movement disorders -- Chapter 12: Autosomal-dominant cerebellar ataxias -- Introduction -- Genetics and molecular pathogenesis.
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Polyglutamine ataxias -- Noncoding repeat expansion/RNA toxicity -- Ion channel dysfunction -- Signal transduction -- Evaluation and management -- Initial evaluation -- Genetic testing -- Treatment and management -- References -- Chapter 13: Autosomal-recessive cerebellar ataxias -- Historic perspectives on the recessive ataxias -- Clinical phenotyping and heterogeneity among the recessive ataxias: -- Genetic classification of the recessive ataxias -- Class I: Friedreich ataxia -- Class II: early-onset recessive ataxias -- Disorders of genomic or mitochondrial DNA metabolism -- Disorders of signal transduction -- Disorders of organelle function -- Disorders of protein quality control -- Disorders of lipid and lipoprotein metabolism -- Disorders of cellular metabolism -- Class III: adolescent-onset recessive ataxias -- Disorders of genomic or mitochondrial DNA metabolism -- Disorders of signal transduction -- Disorders of organelle function -- Disorders of protein quality control -- Disorders of lipid and lipoprotein metabolism -- Class IV: adult-onset recessive ataxias -- Disorders of signal transduction -- Disorders of organelle function -- Disorders of protein quality control -- Disorders of cellular metabolism -- Clinical evaluation, diagnosis, and advances in genetic testing: -- Future directions -- Acknowledgment -- References -- Chapter 14: Genetics of Parkinson disease -- Introduction -- History -- Genetic architecture and known loci -- The PARK loci -- Syndromes of dominantly inherited monogenic PD -- PARK-SNCA -- PARK-LRRK2 -- PARK-VPS35 -- PARK-DNAJC13 and related atypical parkinsonian syndromes -- Syndromes of early-onset, recessively inherited monogenic PD -- PARK-PARKIN -- PARK-PINK1 -- PARK-DJ1 -- Other proposed PD genes -- Genes implicated in association studies -- Genetic testing -- Conclusions and future perspectives -- References.
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Chapter 15: Essential tremor.
Language:
English
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