Genetic Disease Discovery and Therapeutics

PrefaceAcknowledgmentsIDisease classification and possible diagnosis1. Clinical features to consider in a patient with possible genetic diseaseClinical genetics assessment: History and physical examinationFamily history informationResources of information relevant to developmental defects and genetic disordersAspects of developmental delayMovement disorders and cerebral palsyWHO report on recommendations for community genetic services in low and middle income countries (2010)References2. Determining the presence of altered values in clinical laboratory studiesAcutely ill patients in the newborn nursery or patients with possible metabolic diseasePatients with dysmorphologyOrganic acidemias, organic aciduriasClinical utility of genome sequencingExome sequencing and diagnostic value in inborn errors of metabolismReanalysis of sequence dataReferences3. Further laboratory-based investigations for possible gene- or genome-based disordersInvestigations in possible gene or genome-based disordersReferencesIIApplication of therapies and strategies for development of therapies4. Review possible therapies to address clinical manifestations including symptoms and signs and abnormal results of metabolic, biochemical, gene-based microarray or chromosome studiesMitochondrial functions and dysfunctions in mitochondrial disordersPeroxisomes and genetic disorders involving peroxisomesGeneration of stem cell including hematopoietic stem cells for therapyGlycogen storage diseasesReferences5. Review investigations of possible therapies to address underlying disease-related manifestationsInherited disorders of vitamin metabolismBiotinVitamin D hydroxylation deficient rickettsTherapeutic development in specific germline genetic diseasesRange of therapeutic options in lysosomal storage diseasesLysosomal diseases with abnormal storage of mucopolysaccharides and advances in therapyMonoamine neurotransmitter disorders and approaches to therapyEndocrine disordersCongenital adrenal hyperplasiaReferencesFurther reading6. Functional impairments, known genetic disorders, and review reports of established and possible therapies for specific genetic diseasesCiliopathiesNeuronal primary cilia and metabolismPolycystic kidney diseaseMonogenic kidney diseaseInborn errors of immunitySpecific immune disordersNewborn screening for inborn errors of immunitySevere combined immunodeficiencySystemic lupus erythematosusAlpha-1-antitrypsin deficiencyAchondroplasiaHypophosphatasiaHypophosphatasia and hypophosphatemic ricketsCystic fibrosisCystic fibrosis gene mapping and gene product identificationGlycosylationBiometalsDefects in DNA repair processesHearing and deafnessReferencesIIIDiscussion of specific diseases where gene therapy, gene-based therapies or small molecule-based therapies have been successful7. Examples of diseases where appropriate therapies were discoveredEpilepsies: Genetic testing and relevance to treatmentSystemic analysis and reanalysis of exome sequencing data in epilepsyIon channel associated disordersTherapeutic approaches to Duchenne Muscular Dystrophy (DMD)Hemoglobinopathies sickle cell disease, thalassemia advances in treatmentTreatment of sickle cell disease and beta thalassemiaAlpha thalassemia majorSpinal muscular atrophyReferencesFurther reading8. Therapies that address altered gene regulationExamples of disorders due to altered transcription factor activityCraniosynostosisPCSK9 and hyperlipidemiaReferences9. Stem cell review research on therapeutic designUnderstanding of disease mechanisms in promoting therapeutic designStem cells and cell therapiesReferencesIVReview research on therapeutic design10. Review research designed to investigate gene function and possible impact of specific variantsHuntington diseaseTreacher Collins syndrome (TCS)Ribosome biogenesis and ribosomopathiesVision and hearing: The visual cycle, retina and retinitis pigmentosaAge related neurodegenerative conditionsAPOE4 genetic variant and Alzheimer researchReferences11.