CYTOGEN - Shifting 1

• Genetic Disorder


  A disease that is caused by an abnormality in an individual's DNA that also changes a person's DNA
• Range of genetic disorders

  • Small mutation in DNA
  • Additional or subtraction of an entire chromosomes or set of chromosomes
  • Point mutation
  • Insertion
  • Deletion entirely inside one gene due to error in DNA replication or environmental factors such as exposure to teratogens
• Autosomal disorders


  Mutation on the autosomes or numbered chromosomes that carry genes that determine the somatic characteristics and do not have any influence on determining the sex of the individual
• Types of inherited disease

  • Autosomal disorder
  • Allosomal disorder
  • Mitochondrial disorder
• 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 for the disease or trait to develop
• Achondroplasia


  • Disorder of bone growth that prevents the changes of cartilage to bone (long bones of the arms and legs)
  • Short limbs relative to trunk
  • Prominent forehead
  • Low nasal root
  • Redundant skin folds on arms and legs
  • Dwarfism
  • Limited range of motion in the elbows
  • Large head size and small fingers
• Treatment for Achondroplasia


  1. Medication with bone growth or growth hormone

  2. Surgery aimed to correct the spine or bone problems, or reduce pressure inside the brain (hydrocephaly)
• Prognosis for Achondroplasia


  Good, except with cases of spinal compression in the neck
• Hypercholesterolemia


  • Defect in chromosome 19 and a mutation in LDL receptor
  • Impaired uptake of LDL
  • Elevated levels of LDL cholesterol, cardiovascular disease, and stroke
  • Symptoms more severe in homozygous individuals
• Holoprosencephaly


  • Abnormality in brain development wherein the brain does not divide into left and right hemispheres; can also affect head and face development
  • Malformation of the brain (no or reduced evidence of an interhemispheric fissure)
  • Dysmorphic facial features
  • Mental retardation
• Huntington Disease (Huntington Chorea)


  • Progressive motor, cognitive, and psychiatric abnormalities
  • Choria - nonrepetitive, involuntary jerks - is observed in 90% of patients
  • Mutation in Huntingtin gene - CAG Trinucleotide Repeats expansion within the exon
• Marfan Syndrome


  • Abnormalities of disproportionate skeleton, heart, pulmonary system, skin - excessive elasticity, joints - hypermobility
  • Congestive Heart Failure is the frequent cause of death
• Myotonic Dystrophy


  • Muscle Weakness
  • Cardiac Arrhythmias
  • Cataracts
  • Testicular atrophy in males
  • Congenital form - open triangle shape
• Neurofibromatosis I (NF1)


  • Areas of abnormal skin pigmentation includes pale tan, or light brown discoloration, usually under the arms or the groin
  • Numerous benign tumors (neurofibromas) of the peripheral nervous system
  • Malignancy - neurofibrosarcoma, astrocytoma, childhood chronic myelogenous leukemia (CCML)
• Osteogenesis Imperfecta


  • Null mutations - produce milder form of disease
  • Missense mutations - perinatal lethal
  • Disorders - deformed, undermineralized bones subject to frequent fracture
• Polycystic Kidney Disease


  • Cluster of cysts develop in the kidney and interferes with the kidney's ability to filter waste product from the blood
  • Growth of cysts causes kidneys to become enlarged and lead to kidney failure and can also develop in other organs, particularly in the liver
  • Heterozygous individuals - predisposed to PKD because they are likely to lose the second good copy of the genes during their lifetimes
  • Multiple renal cyst
  • End-stage renal disease
  • Kidney Failure
• Cystic Fibrosis


  • Impaired chloride ion channel function
  • Pancreatic insufficiency due to fibrotic lesion
  • Lung infections due to staph. aureus and pseud. aeruginosa
  • Minimizing contact with germs is the top concern for patients
• Test for Cystic Fibrosis

  Chloride sweat test
• Gaucher's Disease


  • Glucocerebroside not adequately degraded, so it builds up in the liver, spleen, bone and nervous system
  • Characterized by splenomegaly, bone and bone marrow infiltration
  • Neurological symptoms are not common
• Hemochromatosis


  • Alters the body to regulate iron absorption
  • Mutation in the HFE gene, located in the chromosome 6
  • One mutation leads to substitution of amino acids - Cystin becomes tyrosine = C282y
  • Enhanced absorption of dietary iron with accumulation of normal, pigmented, iron-protein aggregates (hemosiderin) in the visceral organs
  • Cirrhosis
  • Cardiomyopathy
  • Diabetes
  • Skin pigmentation - most common manifestation
  • Arthritis
• If diagnosed correctly, Hemochromatosis can be treated. Otherwise, it can lead to severe organ damage.
• Phenylketonuria (PKU)


  • Mutation on phenylalanine hydroxylase gene
  • Failure to make enzyme phenylalanine hydroxylase - converts phenylalanine into other compounds such as tyrosine production and produce another cycle to produce tetrahydrobiopterin
  • Mental retardation if untreated possibly due to inhibition of neurotransmitter synthesis
  • Detectable by newborn screening and treatable
• Tay-Sachs Disease


  • Progressive neurodegeneration
  • Seizures
  • Blindness
  • Death by the age of 2
  • Early Indication: Cherry red spot on the retina
• Xeroderma Pigmentosum (XP)


  • Inherited condition that has extreme sensitivity to ultraviolet radiation from sunlight
  • Affects the eyes and areas of the skin exposed to the sun and can also affect the nervous system
  • Gene Defect: Anyone of the nine genes involved in nucleotide excision repair
• Phenylalanine hydroxylase enzyme


  Converts phenylalanine into other compounds such as tyrosine production and produce another cycle to produce tetrahydrobiopterin
• Phenylketonuria (PKU)


  • 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: Hexosaminidase A isoenzyme HEXA
• Tay-Sachs disease


  • Hypotonia
  • Spasticity
  • Seizures
  • Blindness
  • Death by the age of 2
  • Early Indication: Cherry red spot on the retina
• Xeroderma pigmentosum (XP)


  Inherited condition that has extreme sensitivity to UV rays from sunlight
• Xeroderma pigmentosum (XP)


  • Acute Photosensitivity
  • Premature skin aging
  • Premalignant neoplasms of the skin (Basal Cell Carcinoma and/or Squamous Cell Carcinoma)
  • 5% of the patients develop melanoma
  • Patients also exhibit ocular problems due to UV damage
  • 10-to-20-fold increased incidence of internal neoplasm due to inability to repair DNA Damage by endogenously generated and environmental genotoxic agents
• Gene Defect in XP

  Anyone of the nine genes involved in nucleotide excision repair (locus heterogeneity)
• Embryonic development


  1. Streak appears along the back of the embryo

  2. Followed by the connective tissue progenitor cells, notochord, neural tube, heart, central nervous system, arms, legs and other organ rudiments

  3. By week 8, all the organs that will be present in the newborn have begun to develop
• Stages of embryonic development

  • GERMINAL STAGE (First 2 weeks after conception)
  • EMBRYONIC PERIOD (3rd Week to 8th Week)
  • FETAL PERIOD (9th Week to 37th Week)
  • NEONATAL PERIOD (First month after birth)
• Fetal growth


  1. Body proportions approach those of a newborn

  2. Bone replaces softer cartilage

  3. Nerve and muscle functions become coordinated

  4. Sex organs become more distinct by week 6

  5. By week 12, sucks thumb, kicks, makes fists and faces, and has the beginnings of teeth (UNDER THE GUMS)

  6. Fingernails and toenails begin to develop and the external ears are also formed

  7. Vocal cords will be formed by 18 weeks

  8. By the end of the second trimester, the woman feels distinct kicks and jabs and may detect fetal hiccup

  9. In the final trimester, fetal brain cells link into networks as organs elaborate and grow, and fat fills out the skin

  10. The digestive and respiratory systems mature last
• Meconium


  Baby's first bowel movement
• Fetal development at 16 weeks

  1. Muscle tissue and bone continue to form

  2. Skin begins to form

  3. Meconium develops in the baby's intestinal tract

  4. Sucking motions (sucking reflex)

  5. Length: 4 to 5 inches

  6. Weighs: 3 ounces
• Birth defects can be minor or severe
• Critical period


  Time when genetic abnormalities, toxic substances, or viruses can alter a specific structure
• Most birth defects develop during the embryonic period and are more severe than those that arise during the fetal period