Preface Acknowledgments I Disease classification and possible diagnosis 1. Clinical features to consider in a patient with possible genetic disease Clinical genetics assessment: History and physical examination Family history information Resources of information relevant to developmental defects and genetic disorders Aspects of developmental delay Movement disorders and cerebral palsy WHO report on recommendations for community genetic services in low and middle income countries (2010) References 2. Determining the presence of altered values in clinical laboratory studies Acutely ill patients in the newborn nursery or patients with possible metabolic disease Patients with dysmorphology Organic acidemias, organic acidurias Clinical utility of genome sequencing Exome sequencing and diagnostic value in inborn errors of metabolism Reanalysis of sequence data References 3. Further laboratory-based investigations for possible gene- or genome-based disorders Investigations in possible gene or genome-based disorders References II Application of therapies and strategies for development of therapies 4. Review possible therapies to address clinical manifestations including symptoms and signs and abnormal results of metabolic, biochemical, gene-based microarray or chromosome studies Mitochondrial functions and dysfunctions in mitochondrial disorders Peroxisomes and genetic disorders involving peroxisomes Generation of stem cell including hematopoietic stem cells for therapy Glycogen storage diseases References 5. Review investigations of possible therapies to address underlying disease-related manifestations Inherited disorders of vitamin metabolism Biotin Vitamin D hydroxylation deficient ricketts Therapeutic development in specific germline genetic diseases Range of therapeutic options in lysosomal storage diseases Lysosomal diseases with abnormal storage of mucopolysaccharides and advances in therapy Monoamine neurotransmitter disorders and approaches to therapy Endocrine disorders Congenital adrenal hyperplasia References Further reading 6. Functional impairments, known genetic disorders, and review reports of established and possible therapies for specific genetic diseases Ciliopathies Neuronal primary cilia and metabolism Polycystic kidney disease Monogenic kidney disease Inborn errors of immunity Specific immune disorders Newborn screening for inborn errors of immunity Severe combined immunodeficiency Systemic lupus erythematosus Alpha-1-antitrypsin deficiency Achondroplasia Hypophosphatasia Hypophosphatasia and hypophosphatemic rickets Cystic fibrosis Cystic fibrosis gene mapping and gene product identification Glycosylation Biometals Defects in DNA repair processes Hearing and deafness References III Discussion of specific diseases where gene therapy, gene-based therapies or small molecule-based therapies have been successful 7. Examples of diseases where appropriate therapies were discovered Epilepsies: Genetic testing and relevance to treatment Systemic analysis and reanalysis of exome sequencing data in epilepsy Ion channel associated disorders Therapeutic approaches to Duchenne Muscular Dystrophy (DMD) Hemoglobinopathies sickle cell disease, thalassemia advances in treatment Treatment of sickle cell disease and beta thalassemia Alpha thalassemia major Spinal muscular atrophy References Further reading 8. Therapies that address altered gene regulation Examples of disorders due to altered transcription factor activity Craniosynostosis PCSK9 and hyperlipidemia References 9. Stem cell review research on therapeutic design Understanding of disease mechanisms in promoting therapeutic design Stem cells and cell therapies References IV Review research on therapeutic design 10. Review research designed to investigate gene function and possible impact of specific variants Huntington disease Treacher Collins syndrome (TCS) Ribosome biogenesis and ribosomopathies Vision and hearing: The visual cycle, retina and retinitis pigmentosa Age related neurodegenerative conditions APOE4 genetic variant and Alzheimer research References 11. Designing therapies relevant in human genetic disorders Designing therapies for specific diseases Rare diseases, precision medicines, and orphan drug designations Gene editing Crispr CAS9 gene editing Clinical trial designs for rare diseases Pharmacogenetics pharmacogenomics References V Clinical trials design and permissions 12. Clinical trial designs and permissions Human subjects research Bioinformatics and cheminformatics in discovery of new medications CAR T-cell therapy in auto-immune diseases Target discovery through genetic studies and development of therapies References Index

• Considers refined diagnostic techniques for genetic diseases. • Documents evidence regarding mechanisms through which gene defects alter biochemical function and lead to pathology. • Presents new techniques being applied to the treatment of gene and genome-based disorders. • Aims to consider the goals of personalized precision medicine as defined by the NIH.