CYTOGEN AUTOSOMAL 2.0

• GENETIC DISORDER

  is a disease that is caused by an abnormality in an individual’s DNA.

  Range from a small mutation in DNA or additionor subtraction of an entire chromosome or set of chromosomes.

  May result by point mutation or any insertion/ deletion entirely inside one gene
• AUTOSOMES OR SOMATIC CHROMOSOMES

  • carry genes that determine the somatic characteristics and do not have any influence on determining the sex of the individual
  • Appears in pairs
• Autosomal Dominant 


  A pattern of inheritance in which an affected individual has one copy of a mutant gene and one normal gene on a pair of autosomal chromosomes
• Autosomal Recessive


  Two copies of an abnormal gene must be present in order for the disease or trait to develop
• Rules of autosomal dominant inheritance

  • Trait appears in every generation
  • Each child of an affected parent has a one in two chance of being affected
  • Males and females are equally affected
  • Male-to-male transmission 
• Achondroplasia


  Gene defect: Fibroblast growth factor receptor 3 (FGR3)
• Achondroplasia


  Clinical Feature: Short limbs relative to trunk, prominent forehead, low nasal root, redundant skin folds on arms and legs
• Hypercholesterolemia


  Gene defect: LDL receptor
• Hypercholesterolemia


  Clinical Feature: Impaired uptake of LDL, elevated levels ofLDL cholesterol, cardiovascular disease and stroke. Symptomsmore severe in homozygous individuals
• Holoprosencephaly


  Gene defect: Sonic Hedgehog
• Holoprosencephaly


  Clinical Feature: Malformation of the brain (no or reduced evidence of an interhemispheric fissure), dysmorphic facial features, mental retardation
• Huntington Disease (Huntington Chorea)


  Gene defect: Huntingtin (HD) – CAG repeat expansion within exon 1
• Huntington Disease (Huntington Chorea)


  Clinical Feature: Disorder is characterized by progressive motor, cognitive and psychiatric abnormalities. Chorea – nonrepetitive involuntary jerks – is observed in 90% of patients
• Marfan Syndrome


  Gene defect: Fibrillin-1 gene (FBN1) encodes a microfibril-forming connective tissue protein
• Marfan Syndrome


  Clinical Feature: Abnormalities of the skeleton (disproportionate tall stature, scoliosis), heart (mitral valve prolapse, aortic dilatation, dissection of the ascending aorta), pulmonary system, skin (excessive elasticity), and joints (hypermobility). A frequent cause of death is congestive heart failure.
• Myotonic Dystrophy


  Gene defect: A protein kinase gene (DMPK) – CTG repeat expansion in 3’ untranslated region of the gene
• Myotonic Dystrophy


  Clinical Feature: Muscle weakness, cardiac arrhythmias, cataracts and testicular atrophy in males. Children born with congenital formhave a characteristic open triangle-shapedmouth
• Neurofibromatosis 1


  Gene defect: Microdeletion at 17q11.2 involving the NF1 gene
• Neurofibromatosis 1


  Clinical Feature: The disorder is characterized by numerous benign tumors (neurofibromas) of the peripheral nervous system, but a minority of patients also show increased incidence of malignancy (neurofibrosarcoma, astrocytoma, Schwann cell cancers and childhood CML – chronic myelogenous leukemia)
• Osteogenesis Imperfecta


  Gene defect: Either of the genes encoding the α1 or α2 chains of type I collagen
• Osteogenesis Imperfecta


  Clinical Feature: Null mutations produce a milder form of the disease. Missense mutations that act in a dominant negative manner are often perinatal lethal. The disorders are associated with deformed, undermineralized bones that are subject to frequent fracture.
• Polycystic Kidney Disease


  Gene defect: Mutations in either polycystin-1 (PKD1) or polycystin-2(PKD2) gene
• Polycystic Kidney Disease


  Clinical Feature: Heterozygous individuals are predisposed to polycystic kidney disease because they are likely to lose the second good copy of the gene during their lifetime. Multiple renal cysts, blood in urine, end-stage renal disease and kidney failure.
• RULES OF AUTOSOMAL RECESSIVE INHERITANCE

  • Trait appears in siblings, not in their parents or their offsprings
  • On average, 25% of siblings are affected
  • A normal sibling of an affected individual has a 2/3 chance of being the carrier
• Cystic Fibrosis

  Gene defect: Cystic fibrosis transmembrane regulator (CFTR) – impaired chloride ion channel function
• Cystic Fibrosis


  Clinical Feature: Pancreatic insufficiency due to fibrotic lesions, obstruction of lungs due to thick mucus, lung infections (Staph, aureus, Pseud. aeruginosa)
• Gaucher’s disease


  Gene defect: B-Glucosidase
• Gaucher’s disease


  Clinical Feature: Lysosomal storage disease characterized by splenomegaly,hepatomegaly, and bone marrow infiltration. Neurological symptoms are not common
• Hemochromatosis


  Gene defect: Unknown gene on the short arm of chromosome 6
• Hemochromatosis

  Clinical Feature: Enhanced absorption of dietary iron with accumulation of abnormal, pigmented, iron-protein aggregates (hemosiderin) in visceral organs. Cirrhosis, cardiomyopathy, diabetes, skin pigmentation, and arthritis.
• Phenylketonuria


  Gene defect: Usually due to a mutation in Phenylananine hydroxylase (PAH)
• Phenylketonuria


  Clinical Feature: Mental retardation, if untreated, possibly due to inhibition of myelination and disruption of neurotransmitter synthesis. Detectable by newborn screening and treatable
• Tay Sachs Disease


  Gene defect: B-Hexosaminidase (A isoenzyme (HEXA)
• Tay Sachs Disease


  Clinical Feature: Hypotonia, spasticity, seizures, blindness, death by age 2. An early indication is a cherry red spot on the retina.
• Xeroderma pigmentosum


  Gene defect: Anyone of nine genes involved in nucleotide excision repair (locus heterogeneity)
• Xeroderma pigmentosum


  Clinical Feature: Acute photosensitivity, premature skin aging, premalignant actinic keratoses, and benign and malignant neoplasms of the skin, including basal cell carcinoma, squamous cell carcinoma, or both. 5% of patients develop melanomas. Patients also exhibit ocular problems due to UV damage and have a 10- to 20-fold increased incidence of internal neoplasms due to an inability to repair DNA damage by endogenously generated and environmental genotoxic agents.