Genetic Diagnosis of Endocrine Disorders

 
 
Academic Press
  • 2. Auflage
  • |
  • erschienen am 9. Oktober 2015
  • |
  • 472 Seiten
 
E-Book | ePUB mit Adobe DRM | Systemvoraussetzungen
978-0-12-801134-8 (ISBN)
 

Genetic Diagnosis of Endocrine Disorders, Second Edition provides users with a comprehensive reference that is organized by endocrine grouping (i.e., thyroid, pancreas, parathyroid, pituitary, adrenal, and reproductive and bone), discussing the genetic and molecular basis for the diagnosis of various disorders.

The book emphasizes the practical nature of diagnosing a disease, including which tests should be done for the diagnosis of diabetes mellitus in adults and children, which genes should be evaluated for subjects with congenital hypothyroidism, which genetic tests should be ordered in obese patients or for those with parathyroid carcinoma, and the rationale behind testing for multiple endocrine neoplasias.


  • Offers a clear presentations of pharmacogenetics and the actual assays used in detecting endocrine diseases
  • Teaches the essentials of the genetic basis of disease in each major endocrine organ system
  • Offers expert advice from genetic counselors on how to use genetic information in counseling patients
  • Includes new chapters on the genetics of lipid disorders and glycogen storage diseases, genetics of hypoglycemia, and whole genome/exome sequencing
  • Englisch
  • San Diego
  • |
  • USA
Elsevier Science
  • 17,26 MB
978-0-12-801134-8 (9780128011348)
0128011343 (0128011343)
weitere Ausgaben werden ermittelt
  • Cover
  • Title Page
  • Copyright Page
  • Contents
  • List of Contributors
  • Preface to the First Edition
  • Preface to the Second Edition
  • Part I - Introduction
  • Chapter 1 - Mechanisms of Mutation
  • Introduction
  • The types of mutation
  • The mechanisms of mutation
  • Base Pairing and the Action of Mutagenic Agents
  • The Role of Enzymes in Mutation
  • Mismatch Repair
  • Modifiers of Mutation Not Associated with Replication
  • Somatic Hypermutation
  • The role of technology
  • Double-strand break repair-related mechanisms
  • Mobile insertion elements
  • The human mutation rate
  • The phenotypic effect of mutations
  • Conclusion and summary
  • References
  • Part II - Pancreas
  • Chapter 2 - A Clinical Guide to Monogenic Diabetes
  • Introduction
  • Clinical presentation
  • Familial Fasting Hyperglycemia: GCK-Related Hyperglycemia (also Known as GCK-MODY or MODY2)
  • Transcription Factor Diabetes
  • Syndromic Forms of Monogenic Diabetes
  • Neonatal Diabetes Mellitus
  • Transient Neonatal Diabetes
  • Permanent Neonatal Diabetes
  • Genetic testing
  • Exome Testing Options
  • Additional Testing Considerations
  • 6q24-TND Testing
  • Deletion Analysis
  • Intronic Mutations
  • Interpreting Results
  • Genetic Counseling
  • Conclusions
  • References
  • Chapter 3 - Hypoglycemia
  • Introduction
  • Overview of Glucose Homeostasis
  • Background and Incidence/Prevalence
  • Clinical Presentation
  • Diagnostic Evaluation
  • Genetic pathophysiology
  • Hyperinsulinism
  • Hyperinsulinism Resulting from Mutations in ABCC8 or KCNJ11 (Hyperinsulinemic Hypoglycemia, Familial Types 1 and 2) - KATP-HI
  • Hyperinsulinism Resulting from Mutations in GLUD-1 (Hyperinsulinemic Hypoglycemia, Familial 6) - GDH-HI
  • Hyperinsulinism Resulting from Mutations in GCK (Hyperinsulinemic Hypoglycemia, Familial 3) - GK-HI
  • Hyperinsulinism Resulting from Mutations in HADH (Hyperinsulinemic Hypoglycemia, Familial 4) - SCHAD-HI
  • Hyperinsulinism Resulting from Mutations in SLC16A1 (Hyperinsulinemic Hypoglycemia, Familial 7) - Exercise-Induced-HI
  • Hyperinsulinism Resulting from Mutations in INSR (Hyperinsulinemic Hypoglycemia, Familial 5) - Insulin Receptor Activating ...
  • Hyperinsulinism Resulting from Mutations in HNF1A (Hepatocyte Nuclear Factor-1a)
  • Hyperinsulinism Resulting from Mutations in HNF4A (Hepatocyte Nuclear Factor 4-Alpha)
  • Hyperinsulinism Resulting from Mutations in UCP2 (Uncoupling Protein 2)
  • Other Rare Forms of Hypoglycemia Due to Hyperinsulinemia or Related Causes
  • Summary
  • Insulinomas
  • Disorders of Glycogenolysis and Gluconeogenesis - "Glycogen Storage Diseases"
  • Disorders of Glycogenolysis
  • Glycogen Storage Disease Type "0": Glycogen Synthase Deficiency
  • Glycogen Storage Disease Type 1: Von Gierke's Disease (Glucose-6-Phosphatase Deficiency)
  • GSD 1a
  • GSD 1b
  • GSD III (Cori Disease) - Glycogen Debrancher Enzyme Deficiency
  • Glycogen Storage Disease VI (Hers Disease, Glycogen Phosphorylase Deficiency) and GSD IX (Phosphorylase Kinase Deficiency)
  • Disorders of Gluconeogenesis
  • Fructose-1,6-Bisphosphatase (FBPase) Deficiency
  • Phosphoenolpyruvate Carboxykinase (PEPCK) Deficiency
  • Pyruvate Carboxylase Deficiency
  • Other Disorders of Carbohydrate Metabolism
  • Hereditary Fructose Intolerance
  • Galactosemia
  • Defects in Amino Acid Metabolism
  • Maple Syrup Urine Disease (MSUD)/Branched-Chain Amino Aciduria
  • Propionic Acidemia
  • Methylmalonic Acidemia (MMA)
  • Tyrosinemia
  • Fatty Acid Oxidation Disorders
  • Long-Chain Fatty Acid Oxidation Defects
  • Organic Carnitine Transporter 2 (OCTN2) Deficiency
  • Carnitine Shuttle Defects
  • Deficiencies of Mitochondrial Long-Chain Fatty Acid b-Oxidation Enzymes
  • Very Long-Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency
  • Mitochondrial Trifunctional Protein (MTP) Deficiency
  • Multiple Acyl-CoA Dehydrogenase (MAD) Deficiency
  • Medium-Chain Fatty Acid Oxidation Defects
  • Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency
  • Short-Chain Fatty Acid Oxidation Defects
  • Glycerol Metabolism Disorder
  • Disorders of Ketogenesis (Ketone Body Synthesis) and Ketolysis (Ketone Utilization)
  • Disorders of Ketogenesis
  • HMG-CoA Synthase Deficiency185,188
  • HMG-CoA Lyase Deficiency185,189
  • Disorders of Ketolysis185,190
  • Hypoglycemia Due to Counterregulatory Hormone Deficiency
  • Congenital Pituitary Hormone Deficiencies
  • Disorders of the Adrenal Gland
  • Other Counterregulatory Hormone Deficiency Disorders
  • Miscellaneous Disorders Resulting in Hypoglycemia
  • Beckwith-Wiedemann Syndrome (BWS)
  • Russell-Silver Syndrome
  • Sotos Syndrome (Cerebral Gigantism)
  • Congenital Disorders of Glycosylation (CDG)
  • Laron Syndrome
  • Congenital Severe Insulin Resistance Syndromes
  • Primary Generalized Glucocorticoid Resistance
  • Timothy Syndrome
  • AKT2 Mutations
  • Citrin Deficiency
  • Summary
  • References
  • Part III - Pituitary
  • Chapter 4 - Functioning Pituitary Adenomas
  • Introduction
  • Genetic pathophysiology of pituitary adenomas
  • Genetic screening in functioning pituitary adenomas
  • MEN1
  • MEN1-related pituitary tumors
  • Recommendations for Testing in MEN1
  • Carney complex (CNC)
  • CNC-Related Pituitary Tumors
  • Recommendations for Testing in CNC
  • Multiple endocrine neoplasia 4 (MEN4)
  • Recommendations for Testing in MEN4
  • Familial isolated pituitary adenomas (FIPA)
  • Recommendations for AIP Mutation Testing in FIPA and Sporadic Pituitary Adenomas
  • X-Linked Acrogigantism (X-LAG) Syndrome
  • Recommendations for Testing in X-LAG
  • References
  • Chapter 5 - Diabetes Insipidus
  • Introduction
  • Types of diabetes insipidus
  • Familial types of diabetes insipidus
  • Autosomal Dominant FNDI
  • Autosomal Recessive FNDI, Type C
  • X-Linked Recessive NDI
  • Autosomal Dominant/Recessive NDI
  • Clinical diagnosis
  • Genetic testing
  • Which Gene to Test?
  • Diagnostic Genetic Testing
  • Presymptomatic Genetic Diagnosis in FNDI
  • Genetic Testing in Individuals at Risk of Being Carriers
  • Prenatal Genetic Diagnosis
  • Available Laboratories and Resources
  • References
  • Chapter 6 - States of Pituitary Hypofunction
  • Introduction
  • Genetic pathophysiology
  • Diagnosis, genetic testing, and interpretation
  • Treatment
  • References
  • Part IV - Thyroid
  • Chapter 7 - Congenital Defects of Thyroid Hormone Synthesis
  • Introduction
  • Pathophysiology and genetics of specific dyshormonogenesis defects
  • Defect in Thyroidal Iodide Trapping - Gene: SLC5A5 (NIS)
  • Defect in Efflux of Iodide Across the Apical Thyroid Cell Membrane - Gene: SLC26A4 (PDS)
  • Defect in the Follicular Matrix Protein Providing Tyrosyl Groups for Iodide Organification - Gene: TG
  • Defects in the Enzymes Required for Iodide Organification
  • Defect in the Key Enzyme Catalyzing the Iodination and Coupling of Tyrosyl Moieties - Gene: TPO
  • Defect in the NADPH-oxidase Providing Hydrogen Peroxide for TPO - Gene: DUOX2 (THOX2)
  • Defect in the DUOX2 Cofactor - Gene: DUOXA2
  • Defect in Iodide Recycling with Secondary Iodide Deficiency - Gene: IYD (DEHAL1)
  • Availability of genetic testing
  • Conclusions
  • Acknowledgment
  • References
  • Chapter 8 - Developmental Abnormalities of the Thyroid
  • Introduction
  • TSH receptor gene mutations (loss of function)
  • PAX8 gene mutations
  • TTF1/NKX2-1 gene mutations
  • TTF2 (FOXE 1 or FKHL15) gene mutations
  • GLIS3 gene mutations
  • NKX2-5 gene mutations
  • Syndromes associated with CH from thyroid dysgenesis
  • TSHR gene mutations (gain of function)
  • Treatment
  • Conclusions
  • References
  • Chapter 9 - Syndromes of Impaired Sensitivity to Thyroid Hormone
  • Introduction
  • Overview of described and putative defects in syndromes of impaired sensitivity to thyroid hormone
  • Thyroid Hormone Cell Transport Defect (THCTD)
  • Thyroid Hormone Metabolism Defect (THMD)
  • Abnormal Hormone Transfer to the Nucleus
  • Thyroid Hormone Receptor Defects Resulting in RTH
  • Abnormal Cofactors or Interfering Substances
  • "Nongenomic" Abnormalities
  • Resistance to thyroid hormone (RTH)
  • Background
  • RTHb
  • Incidence and Prevalence
  • Clinical Features
  • Laboratory Findings and Differential Diagnosis
  • Genetic Pathophysiology
  • Treatment
  • NonTR-RTH
  • RTHa
  • Background, Incidence, and Prevalence
  • Clinical Features
  • Laboratory Findings and Differential Diagnosis
  • Genetic Pathophysiology
  • Treatment
  • Thyroid hormone cell transporter defect
  • Background, Incidence, and Prevalence
  • Clinical Features
  • Laboratory Findings
  • Genetic Pathophysiology
  • Treatment
  • Thyroid hormone metabolism defect
  • Background, Incidence, and Prevalence
  • Clinical Features
  • Laboratory Findings and Differential Diagnosis
  • Genetic Pathophysiology
  • Treatment
  • References
  • Chapter 10 - Molecular Diagnosis of Thyroid Cancer
  • Introduction
  • Oncogene rearrangements
  • RET/PTC
  • TRK
  • ALK
  • PAX8/PPARg
  • Gene mutations
  • RAS Isoforms
  • BRAF Oncogene
  • hTERT
  • Other genetic alterations
  • TP53
  • b-Catenin
  • PI3KCA
  • AKT1
  • IDH1
  • Epidermal Growth Factor Receptor
  • Application of molecular findings to the clinical diagnosis of thyroid cancer
  • Search of Oncogene Mutations
  • Gene Expression Profiling
  • miRNAs in thyroid lesions
  • Microarray
  • mRNA expression
  • Conclusion
  • References
  • Part V - Parathyroid/Bone
  • Chapter 11 - Genetics of Hyperparathyroidism Including Parathyroid Cancer
  • Introduction
  • Hyperparathyroidism-jaw tumor syndrome (HPT-JT), HRPT2, and parathyroid carcinoma
  • Introduction
  • Genetic Pathophysiology
  • Diagnosis Genetic Testing and Interpretation
  • Treatment
  • Familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT)
  • Introduction
  • Genetic Pathophysiology
  • Diagnosis Genetic Testing and Interpretation
  • Treatment
  • Autosomal dominant hypoparathyroidism
  • Familial isolated hyperparathyroidism
  • Introduction
  • Genetic Pathophysiology
  • Diagnosis Genetic Testing and Interpretation
  • Treatment
  • Summary
  • References
  • Chapter 12 - Genetic Diagnosis of Skeletal Dysplasias
  • Introduction
  • Sclerosing bone disorders
  • Osteopetrosis
  • Clinical Presentation
  • Radiography
  • Laboratory Tests
  • Histology
  • Genetic Pathophysiology
  • Genetic Diagnostic Testing21
  • Treatment
  • Progressive Diaphyseal Dysplasia
  • Clinical
  • Radiography
  • Laboratory
  • Histology
  • Genetics and Pathophysiology
  • Genetic Diagnostic Testing and Interpretation
  • Treatment
  • Pyknodysostosis
  • Clinical
  • Radiography
  • Laboratory
  • Histology
  • Genetic Pathophysiology
  • Diagnosis
  • Treatment
  • Hyperostosis Corticalis Generalisata
  • Clinical
  • Histology
  • Radiography
  • Laboratory
  • Genetic Pathophysiology
  • Genetic Diagnostic Testing
  • Treatment
  • Melorheostosis
  • Clinical
  • Histology
  • Radiography
  • Laboratory
  • Genetic Pathophysiology
  • Genetic Diagnostic Testing
  • Treatment
  • High Bone Mass Phenotype
  • Juvenile Paget's Disease
  • Osteopathia Striata
  • Osteopoikilosis
  • Radiographic Findings
  • Histology
  • Genetic Findings
  • Disorders of defective mineralization
  • Axial Osteomalacia
  • Clinical Features
  • Radiologic Changes
  • Laboratory
  • Pathogenesis and Histology
  • Genetic Pathophysiology and Diagnosis
  • Treatment
  • Hypophosphatasia
  • Clinical
  • Pathogenesis
  • Laboratory Tests
  • Genetic Testing
  • Treatment
  • Vitamin D-Dependent Rickets Types I and II
  • Dysplasias of bone and cartilage with normal or low bone mass
  • Achondroplasias
  • Diagnosis
  • Treatment
  • Multiple Exostoses
  • Clinical
  • Radiographic Features
  • Pathophysiology and Genetic Basis
  • Treatment
  • Osteogenesis Imperfecta
  • Clinical
  • Laboratory
  • Radiology and Imaging
  • Pathophysiology
  • Genetic Testing
  • Treatment
  • Pachydermoperiostosis (Hypertrophic Osteoarthropathy)
  • Clinical
  • Radiographic Features
  • Laboratory Testing
  • Treatment
  • References
  • Chapter 13 - Vitamin D Disorders
  • Introduction
  • Calcium, phosphorus, and vitamin D metabolism
  • Vitamin D deficiency and rickets
  • Genetic causes of rickets - osteomalacia: disorders in vitamin D metabolism and recognition
  • Vitamin D-25 Hydroxylase Deficiency
  • Vitamin D-Dependent Rickets Type I: Pseudovitamin D Deficiency Rickets (PDDR)
  • Vitamin D-Dependent Rickets Type II: Hereditary Vitamin D Resistant Rickets (HVDRR)
  • Vitamin D-Dependent Rickets Type III
  • Treatment Strategies for Vitamin D Resistant Rickets
  • Genetic causes of rickets: hypophosphatemic disorders
  • X-Linked Hypophosphatemic Rickets (XLH)
  • Autosomal Dominant Hypophosphatemic Rickets (ADHR)
  • Treatment Strategies
  • Genetic causes of hypercalcemia associated with alterations in vitamin D metabolism
  • Idiopathic Infantile Hypercalcemia
  • Treatment Strategies
  • References
  • Part VI - Adrenal
  • Chapter 14 - Congenital Adrenal Hyperplasia
  • Introduction
  • Background, Incidence, Prevalence
  • Steroid 21 Hydroxylase Deficiency (21-OHD)
  • Genetic pathophysiology
  • Pathophysiology of Mutations
  • Diagnosis: genetic testing and interpretation
  • Interpretation of Test Results
  • Complexity of the Active Genes and Their Nearby Pseudogenes
  • Phenotype-Genotype Correlation
  • Prenatal Diagnosis and Treatment of 21-OHD CAH
  • Treatment
  • The Effect of Genetic Information in Treatment Decision
  • Genetic Counseling
  • Risk for the Offspring of a Proband
  • Recommendation for Diagnosis and Treatment
  • Resources
  • References
  • Chapter 15 - Genetics of Adrenocortical Tumors (ACT) and Hypersecretory Syndromes
  • Introduction
  • The Li-Fraumeni Syndrome: TP53 and Locus 17p13
  • The Beckwith-Wiedemann Syndrome: IGF-II (Insulin-Like Growth Factor II) and 11p15 Alterations
  • Multiple Endocrine Neoplasia Type 1: The Menin Gene and Locus 11q13
  • The Carney Complex: PRKAR1A Gene and Locus 17q22-24
  • Familial Adenomatous Polyposis (FAP) and the ß-Catenin Gene
  • and the Lynch Syndrome
  • The McCune-Albright Syndrome: GNAS1 Gene
  • Congenital Adrenal Hyperplasia
  • Glucocorticoid-Remediable Aldosteronism
  • ACTH Receptor (ACTH-R) Gene
  • ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH)
  • Sporadic Adrenocortical Adenomas With Cushing's Syndrome
  • Integrated Genomic Organization of ACCs
  • Conclusions
  • Acknowledgments
  • References
  • Chapter 16 - Hereditary Syndromes involving Pheochromocytoma and Paraganglioma
  • Multiple endocrine neoplasia type 2
  • Von Hippel-Lindau syndrome (VHL)
  • Neurofibromatosis type 1
  • Hereditary paraganglioma/pheochromocytoma syndromes
  • Genetic risk assessment in patients with apparently sporadic pheochromocytoma
  • Authors' Recommended Genetic Testing Strategy for Patients with Apparently Sporadic Pheochromocytoma/Paraganglioma
  • Summary
  • References
  • Chapter 17 - Genetic Conditions Associated with Congenital Adrenocortical Insufficiency or Glucocorticoid and/or Mineralocortico...
  • Introduction
  • Genetics of embryology and function of the adrenal glands
  • Genetic defects causing CAI: an overview and a comment on treatment
  • CAI Associated with Hypothalamic-Pituitary-Adrenal (HPA) Axis Defects
  • CAI Associated with Primary Adrenocortical Development Defects
  • CAI Associated with Metabolic Disorders
  • CAI Associated with Adrenal Calcifications and/or Hemorrhage: Genetic Factors
  • CAI Associated with Genetic Defects Leading to Autoimmunity
  • Treatment
  • Specific genetic conditions associated with CAI
  • Congenital Isolated ACTH Deficiency
  • ACTHR Defects (Familial Glucocorticoid Deficiency 1, FGD-1)
  • Other Genetic Defects for Familial Glucocorticoid Deficiency Type-2 (FGD-2)
  • Allgrove or Triple-A Syndrome
  • Adrenal Hypoplasia Congenita (AHC)
  • X-Linked Adrenoleukodystrophy (X-ALD)
  • APECED (MEA-1)
  • Genetic conditions associated with resistance to glucocorticoids or mineralocorticoids
  • Primary Familial or Sporadic Generalized Glucocorticoid Resistance
  • Pseudohypoaldosteronism (Type-I)
  • Acknowledgment
  • References
  • Part VII - Reproductive
  • Chapter 18 - Genetic Considerations in the Evaluation of Menstrual Cycle Irregularities
  • Introduction
  • Ovarian disorders
  • Primary Ovarian Insufficiency
  • X-Chromosome Abnormalities
  • Turner's Syndrome
  • Trisomy X
  • Deletions
  • Translocations
  • POI Genes on the X Chromosome
  • Fragile X Metal Retardation (FMR1) Gene
  • Bone Morphogenetic Protein 15 Gene (BMP15)
  • Autosomal Genes
  • Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome (BPES)
  • Inhibin (INH) Gene
  • Galactose-1-Phosphate Uridyltransferase (GALT) Gene
  • Folliculogenesis Specific Basic Helix-Loop-Helix Gene Mutation (FIGLA gene)
  • NOG Gene Mutations Causing Noggin Deficiency
  • The Estrogen Receptor (ER)
  • Down Syndrome
  • Polycystic Ovary Syndrome
  • CYP11A Gene
  • Chromosome 19p13.2 PCOS Susceptibility Locus (D19S884)
  • The Androgen Receptor Gene
  • Adrenal disorders
  • Nonclassic Congenital Adrenal Hyperplasia
  • Clinical and laboratory evaluation
  • Conclusions
  • References
  • Chapter 19 - Disorders of Sex Development
  • Disorders of sex development
  • Disorders of sex determination
  • 46,XY Disorders
  • Gonadal Dysgenesis
  • Presentation and Diagnosis
  • 46,XX Disorders
  • Testicular and Ovotesticular DSD
  • Presentation and Diagnosis
  • Sex Chromosome Disorders
  • Turner Syndrome
  • Presentation and Diagnosis
  • Klinefelter Syndrome
  • Presentation and Diagnosis
  • Disorders of sex differentiation
  • Disorders in Testosterone Biosynthesis
  • Congenital Adrenal Hyperplasia
  • Presentation and Diagnosis
  • Congenital Lipoid Adrenal Hyperplasia
  • Presentation and Diagnosis
  • Defects in 5a-Reductase Type 2
  • Presentation and Diagnosis
  • 3a-Reductase, AKR1C2 (Backdoor Pathway of DHT Synthesis)
  • Presentation and Diagnosis
  • Defects in Androgen Activity
  • Complete and Partial AIS
  • Presentation and Diagnosis
  • Gonadotropin and Gonadotropin Receptor Defects
  • Leydig Cell Hypoplasia/Agenesis
  • Presentation and Diagnosis
  • LHCGR Mutations in 46,XY Precocious Puberty
  • Presentation and Diagnosis
  • LHCGR Mutations in 46,XX Patients
  • Presentation and Diagnosis
  • FSHR Mutations in Ovarian Hyperstimulation Syndrome (OHSS)
  • Presentation and Diagnosis
  • FSHR Mutations in 46,XX Ovarian Dysgenesis
  • Presentation and Diagnosis
  • FSH Inactivating Mutations
  • Presentation and Diagnosis
  • Disorders of AMH or AMH Receptor
  • Persistent Müllerian Duct Syndrome
  • Presentation and Diagnosis
  • Androgen Excess: Fetoplacental Causes
  • P450 Aromatase Deficiency
  • Presentation and Diagnosis
  • P450 Oxidoreductase Deficiency
  • Androgen Excess: Maternal Etiologies
  • High-throughput sequencing in the diagnosis of disorders of sex determination
  • Conclusions
  • References
  • Chapter 20 - Androgen Insensitivity Due to Mutations of the Androgen Receptor
  • Male phenotypic development is controlled by androgens
  • The androgen receptor
  • Measurements of AR and its function
  • The modulation of gene expression by the AR
  • Androgen insensitivity: a spectrum of abnormalities caused by defects of the AR
  • The genetic basis of androgen insensitivity
  • Disruption of the primary amino acid sequence
  • Alterations of the DBD
  • Alterations of LBD structure
  • Mutations within the amino terminus
  • Mutations that cause decreased levels of ligand binding
  • Phenotype and genotype in patients with various forms of androgen insensitivity
  • Spinal and bulbar muscular atrophy and prostate cancer
  • Diagnostic resources
  • References
  • Part VIII - Adipocyte
  • Chapter 21 - Obesity
  • Introduction
  • Background, Incidence, Prevalence
  • Clinical Presentation
  • Genetic pathophysiology
  • Monogenic Obesity
  • Melanocortin 4 and 3 Receptor-Linked Obesities
  • Obesity Syndromes
  • Diagnosis genetic testing and interpretation
  • Monogenic Obesity
  • Melanocortin 4 Receptor-Linked Obesity
  • Obesity Syndromes
  • Treatment
  • Monogenic Obesity
  • Melanocortin 4 Receptor-Linked Obesity
  • Obesity Syndromes
  • Bariatric Surgery
  • References
  • Chapter 22 - Syndromes of Severe Insulin Resistance and/or Lipodystrophy
  • Introduction
  • Background, Incidence, Prevalence
  • Clinical Presentation
  • Primary Insulin Signaling Defects
  • Lipodystrophy
  • Complex Syndromes
  • Genetic pathophysiology
  • Known INSR Mutations and Specific Phenotypes
  • Pathophysiology of Genetic Insulin Receptoropathies
  • Known AGPAT2 and BSCL2 Mutations and Specific Phenotypes
  • Pathophysiology of Congenital Generalized Lipodystrophy
  • Known LMNA Mutations and Specific Phenotypes
  • Pathophysiology of LMNA-Associated Lipodystrophy
  • Known PPARG Mutations and Specific Phenotypes
  • Pathophysiology of PPARG-Associated Lipodystrophy
  • Diagnosis, genetic testing, and interpretation
  • Which Tests are Best to Order in Whom?
  • Labs Available for Testing
  • Lists of Consultants and Resources
  • Predictive Value of Test
  • INSR
  • Lipodystrophy
  • Significance of Negative Test
  • Should Family Members be Tested?
  • Treatment
  • Based on the Genetic Information, How Does That Affect Treatment, If At All?
  • Genetic Counseling and Prenatal Testing
  • References
  • Chapter 23 - Lipodystrophies
  • Introduction
  • Autosomal recessive lipodystrophies
  • Congenital Generalized Lipodystrophy (CGL)
  • CGL Type 1: AGPAT2 Mutations
  • CGL Type 2: BSCL2 Mutations
  • CGL Type 3: Caveolin 1 Mutations
  • CGL Type 4: PTRF Mutations
  • Molecular Diagnosis
  • Differential Diagnosis
  • Mandibuloacral Dysplasia (MAD)-Associated Lipodystrophy
  • MAD Type A Due to LMNA Mutations
  • MAD, Type B Associated with Zinc Metallopeptidase STE24 (ZMPSTE24) Mutations
  • Molecular and Differential Diagnosis
  • Mandibular Hypoplasia, Deafness, Progeroid Features (MDP)-Associated Lipodystrophy Syndrome
  • Autoinflammatory Lipodystrophy Syndrome
  • Short Stature, Hyperextensibility of Joints and/or Inguinal Hernia, Ocular Depression, Reiger Anomaly, and Teething Delay (...
  • Neonatal Progeroid Syndrome (Wiedemann-Rautenstrauch Syndrome)
  • Familial Partial Lipodystrophy (FPLD) Due to CIDEC Mutation
  • Autosomal dominant lipodystrophies
  • Familial Partial Lipodystrophies (FPLD)
  • Type 1 Kobberling Variety (FPLD1-unknown)
  • Type 2 FPLD, Dunnigan Variety (FPLD2: LMNA Mutations)
  • Type 3: FPLD Associated with PPARG Mutations
  • Type 4: FPLD Associated PLIN1 Mutations
  • Type 6 FPLD Associated with AKT2 Mutations
  • Other Types of FPLD
  • Molecular Diagnosis
  • Differential Diagnosis
  • Atypical Progeroid Syndrome Due to LMNA Mutations
  • Hutchinson-Gilford Progeria Syndrome (HGPS)
  • Other Extremely Rare Subtypes
  • Overall Diagnostic Approach
  • Availability of Genetic Testing
  • Predictive Value of the Genetic Testing and Genetic Counseling
  • References
  • Part IX - Multisystem Disorders
  • Chapter 24 - Multiple Endocrine Neoplasia Type 1 (MEN1)
  • Introduction
  • Background, Prevalence
  • Natural History
  • Clinical Presentation, Diagnosis, and Treatment
  • Parathyroid Adenoma
  • Phenocopies
  • Diagnosis
  • Tumors of the Endocrine Duodenum and Pancreatic Islets
  • Definition Neuroendocrine Tumors
  • Symptomatology
  • Absence of Symptoms
  • Diagnosis
  • Specific Syndromes
  • Zollinger-Ellison Syndrome (ZES)
  • Surgery
  • Other Functioning Pancreatic Islet Cell Tumors
  • VIP, Somatstatin, Glucagonoma, and WDHA
  • Growth Hormone-Releasing Hormone (GHRH)-Producing Tumors
  • Pituitary Adenomas
  • Symptomatology
  • Diagnosis
  • Adrenal Tumors
  • Neuroendocrine Tumors of Thymus, Lungs, and Stomach
  • Imaging
  • Thymus
  • Lung (NETs)
  • Gastric (NETs)
  • Genetic pathophysiology of MEN1
  • Known Mutations and Specific Phenotypes
  • Pathophysiology of Mutations (How They Cause the Disease)
  • Normal Function of the Intact MEN1 Gene Product
  • Loss of Menin Function and Tumor Growth
  • Null Mutant Animals
  • Familial Aberrant Expression (Burin)
  • More Malignant Forms or Aggresive Forms with Loss of Menin
  • Sporadic MEN1-Related Tumors
  • Sporadic Parathyroid Adenoma
  • Sporadic Pituitary Adenoma
  • Sporadic Pancreatic NETs
  • Common Pathways in Multistep Carcinogenesis
  • MEN1 mutation analysis
  • Methods for MEN1 Mutation Analysis
  • Interpretation of Results of MEN1 Gene Mutation Analysis
  • Selection of Individuals Eligible for MEN1 Gene Mutation Testing
  • Laboratories Available for Genetic Testing
  • Prenatal Testing
  • Predictive Value of Testing
  • MEN1 Genetic Screening in Apparently Sporadic Tumors
  • Significance of a Negative Test
  • Treatment
  • Based on Genetic Information: How Does it Affect Treatment?
  • Genetic Counseling
  • Recommendations for the future
  • Conclusions
  • Acknowledgment
  • References
  • Chapter 25 - Genetics of Polyglandular Failure
  • Definition, incidence, prevalence
  • Clinical spectrum
  • Genetic pathophysiology
  • Known Mutations/Polymorphisms and Specific Phenotypes
  • Pathophysiology of Mutation
  • APS1
  • APS2/3
  • Diagnosis, genetic testing, and interpretation
  • Which Tests are Best to Order in Whom?
  • Laboratories Available for Genetic Testing
  • Prenatal Testing
  • Lists of Resources
  • APS1 Resources
  • Predictive Value of Test
  • Significance of Negative Test
  • Should Family Members be Tested?
  • Management
  • How Does the Genetic Information Affect Treatment, if at All?
  • Genetic Counseling
  • References
  • Part X - Growth
  • Chapter 26 - Genetic Diagnosis of Growth Failure
  • Introduction
  • Background, Incidence, Prevalence
  • Clinical Presentation
  • Genetic pathophysiology
  • Known Mutations and Specific Mutations
  • Mutations/Deletions of GHR
  • Mutations of STAT5B
  • Mutations/Deletions of IGF1
  • Mutations of IGFALS
  • Mutations of IGF1R
  • Diagnosis: genetic testing and interpretation
  • Which Tests are Best to Order in Whom?
  • Labs Available for Testing
  • Prenatal Testing?
  • Lists of Consultants and Resources
  • Predictive Value of a Test?
  • Significance of a Negative Test?
  • Should Family Members be Tested?
  • Treatment
  • Based on the Genetic Information, How Does that Affect Treatment, if at All?
  • Genetic Counseling
  • References
  • Part XI - Miscellaneous
  • Chapter 27 - Cost-Effectiveness of Genetic Testing for Monogenic Diabetes
  • Cost of diabetes care
  • Heterogeneity of diabetes mellitus
  • Monogenic diabetes
  • Precision medicine in monogenic diabetes
  • Neonatal Diabetes
  • MODY
  • Considerations in genetic testing for monogenic diabetes
  • The role of cost-effectiveness analysis in healthcare
  • Cost-effectiveness analysis of monogenic diabetes
  • Cost-Effectiveness Analysis in Neonatal Diabetes
  • Policy Decision
  • Model for Diabetes Complications
  • Impact of Neonatal Diabetes Genetic Testing
  • Cost-Effectiveness Analysis in MODY
  • Policy Decision
  • Models for Diabetes Complications
  • Impact of MODY Genetic Testing
  • Future studies of cost-effectiveness analysis in monogenic diabetes
  • Conclusions
  • References
  • Chapter 28 - Genetic Counseling: The Role of Genetic Counselors on Healthcare Provider and Endocrinology Teams
  • Introduction
  • The genetic counseling profession
  • The role of genetic counselors on the healthcare provider team
  • The Role of Genetic Counselors on the Endocrinology Team
  • The genetic counseling process
  • The pedigree: medicine and art
  • Pedigree analysis and risk perception
  • Penetrance
  • Expressivity
  • Negative Family History
  • Risk Perception
  • Summary
  • References
  • Chapter 29 - Setting Up a Laboratory
  • Introduction
  • Regulations for diagnostic genetic laboratories
  • The Sources of Regulation
  • Enforcement of Regulations
  • Inspections
  • Proficiency Testing
  • Laboratory-Developed Tests
  • HIPAA
  • Intellectual Property
  • The preanalytic phase
  • The Testing Process Overview
  • Requisition
  • Sample Types
  • Specimen Identification and Log-in
  • DNA preparation
  • Cell Handling
  • DNA/RNA Purification
  • Automated Extractors
  • DNA (RNA) Quantitation
  • Nucleic Acid Integrity
  • Sample Storage
  • Analytic phase
  • Assay Validation
  • Procedure Manual
  • Reagents
  • Controls
  • Confirmatory Assays
  • Data Retention and Storage
  • Methods - general PCR
  • Thermocyclers
  • Minimizing PCR Amplicon Contamination
  • Methods - real-time and digital PCR29
  • Double-Stranded DNA Binding Dyes
  • Hydrolysis Probes
  • Hybridization Probes
  • Real-Time PCR Instrumentation
  • Digital PCR
  • Methods - microarrays
  • Methods - methylation analysis
  • Methods - sequencing
  • First-Generation Sequencing
  • Second-Generation Sequencing (NGS)
  • Overview
  • Instrumentation Overview
  • Library Preparation for NGS
  • Whole Genome Sequencing
  • Pull-Down Including "Whole Exome" Sequencing
  • Amplicon Resequencing
  • Notes on the Different Approaches
  • Library Automation
  • Bioinformatics for NGS
  • Quality assurance for NGS
  • General hardware and software considerations
  • Computers
  • Laboratory Management Software
  • General Purpose DNA Analysis Software
  • Sanger Sequencing Software
  • NGS Software
  • Data Formats
  • Commercial Software
  • Variant Annotation/Interpretation
  • Performance
  • Postanalytic phase
  • Assay Review
  • Interpretation and Reporting
  • Interpretation
  • Incidentalomas
  • Reporting
  • Summary
  • References
  • Chapter 30 - Introduction to Applications of Genomic Sequencing
  • Overview
  • From human genetics to genomics
  • Excess of rare variation in the human genome
  • Data sharing becomes essential
  • PNPLA6 gene identification - an example for a number of trends in genomics
  • Conclusions
  • References
  • Index
  • Back Cover

Dateiformat: EPUB
Kopierschutz: Adobe-DRM (Digital Rights Management)

Systemvoraussetzungen:

Computer (Windows; MacOS X; Linux): Installieren Sie bereits vor dem Download die kostenlose Software Adobe Digital Editions (siehe E-Book Hilfe).

Tablet/Smartphone (Android; iOS): Installieren Sie bereits vor dem Download die kostenlose App Adobe Digital Editions (siehe E-Book Hilfe).

E-Book-Reader: Bookeen, Kobo, Pocketbook, Sony, Tolino u.v.a.m. (nicht Kindle)

Das Dateiformat EPUB ist sehr gut für Romane und Sachbücher geeignet - also für "fließenden" Text ohne komplexes Layout. Bei E-Readern oder Smartphones passt sich der Zeilen- und Seitenumbruch automatisch den kleinen Displays an. Mit Adobe-DRM wird hier ein "harter" Kopierschutz verwendet. Wenn die notwendigen Voraussetzungen nicht vorliegen, können Sie das E-Book leider nicht öffnen. Daher müssen Sie bereits vor dem Download Ihre Lese-Hardware vorbereiten.

Weitere Informationen finden Sie in unserer E-Book Hilfe.


Download (sofort verfügbar)

85,62 €
inkl. 19% MwSt.
Download / Einzel-Lizenz
ePUB mit Adobe DRM
siehe Systemvoraussetzungen
E-Book bestellen

Unsere Web-Seiten verwenden Cookies. Mit der Nutzung dieser Web-Seiten erklären Sie sich damit einverstanden. Mehr Informationen finden Sie in unserem Datenschutzhinweis. Ok