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Flashcards in Pathology: Genetics Deck (45):


*Any chromosomal disorder not on the sex genes.


^Genetic heterogeneity

*Single phenotype caused by any number of genetic variations


^Why are enzymatic mutations more impacted by recessive genes?

*Both chromosomes are affected. The other chromosome cannot compensate for loss of enzyme function.


^Why are regulatory systems more prone to dominant genes?

*The dominant gene usually presents with a negative effect. Mixing 1 part toxin with 1 part water. The toxin will dominate your response as you die.


^Polygenic diseases

*Many genes contribute to the overall condition of disease.


^Clinical presentations of Turner's Syndrome

*No development of secondary sex characteristics, amenorrhea (menopause before menarche), and webbed neck. Distended lymph vessels also causes edema and congenital heart failure.



*Autosomal recessive genetic mutation in the noncoding region that affects alpha/beta subunit synthesis. Consequently gamma subunit is produced, builds up in RBCs and kills them.


^Thallacemia Clinical Symptoms

*Anemia due to decreased Hgb function.



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*Hydrops fetalis. Severe anemia results in hypoxia. Hypoxia damages the liver. The liver doesn't produce albumin and presents edema.



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*Anemia induces release of erythropoetiin in thalassemia. Erythropoietin causes bone marrow to expand to compensate for decreased RBC function.


^Why is Autosomal Polycystic Kidney Disease dominant?

*The mutation is in PKD1 and PKD2 for genes that produce polycystin 1 and 2 proteins. This protein is a signaling protein in the tubules that signals pressure levels. Mutations result in fluid accumulation and development of fluid filled cysts later in life.


^What condition is related to development of berry aneurisms?

*Autosomal Polycystic Kidney Disease. 10-30% of patients get this in the cerebral Circle of Willis.



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*Autosomal Polycystic Kidney Disease.


^Hurler's Syndrome Enzyme Deficiency

*alpha-1-iduronidase. Deficiency results in mucopolysaccharide accumulation in cells because it cannot be metabolized.


^How is accumulation of mucopolysaccharides pleiotropic?

*Its accumulation leads to widespread problems in all organ systems. Skeletal and gross morphologic deformities are prominent.


^Why is a cherry red spot prominent in lysosomal disorders?

*Lysosomes fill up with indigestible substance and turn pale. Vessels around them look more red.


^What are the mucopolysaccharidosis metabolites and where do they accumulate?

*Heparin sulfate and dermatan sulfate. They accumulate in the subendothelial cell lysosomes of arteries in the CNS or heart.


^Clinical features of mucopolysaccharidosis.

*Hepatosplenomegaly, coarse facial features, skeletal deformities, lesions in the brain and valvular lesions.


^Tay-Sachs enzyme deficiency, metabolite accumulate and target tissue

*Enzyme = alpha-hexosaminidase, Accumulate = gangliosides, Target tissue = neurons


^Tay-Sachs clinical manifestations

*Motor and mental deterioration = flaccidity, blindness, dementia and death by age 2-3.


^Niemann-Pick A and B enzyme deficiency, metabolite accumulate and target tissue

*Enzyme = sphingomyelinase, Accumulate = sphingomyelin, Type A = CNS, Type B = All other organs


^Niemann-Pick A & B clinical manifestations

*Infant with hepatosplenomegaly, lymphadenopathy, bone marrow infiltrate, psychomotor deterioration, failure to thrive, vomiting and fever. Cherry red spot and death by 3 years old.


^Niemann-Pick C mutation, accumulate and symptoms

*Mutation = NPC1 and NPC 2 receptors, Accumulate = cholesterol inside lysosomes, Symptoms = ataxia, dystonia and psychomotor regression


^Gaucher enzyme deficiency, accumulate and target tissue

*Enzyme = glucocerebrosidase, Accumulate = glucocerebrosides, Target tissue = spleen and bone marrow


^Gaucher clinical manifestations

*Bones that break easily due to bone erosion by macrophage activity. Hypersplenism. Pancytopenia. Thrombocytopenia.



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*Alcian blue stain of mucopolysaccharides.



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*Cytoplasmic clearing typical of lysosomal storage disorders.



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*Alder-Reilly anomaly. Mucopolysaccharides stain a deep granular purple in blood leukocytes.


^How is hypercholesterolemia developed genetically?

*Mutations in LDL receptors in hepatocytes increase the amount of LDL circulating in the plasma. When both genes are defective, disease manifestation worsens.



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*Cholesterol-filled macrophages accumulating under the skin in xanthoma.



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Xanthoma. Cholesterol accumulation under the skin.


^Down's Syndrome Clinical Manifestations

*Clinodactyly of 5th finger, Simeon creases, Epicanthal folds, Slanted palpebral fissures, intestinal atresia


^Why do patients with down syndrome have higher incidence of Alzheimer's and leukemia?

*Genes coding for amyloid precursor protein and leukemia are on chromosome 21. This is due to over expression of these genes.


^How does intracellular cholesterol affect the cell?

*Inhibits HMG CoA Reductase = inhibition of cellular cholesterol production, Activates acyl CoA = activates cholesterol storage, Decreases LDL receptor production


^Glycogen storage disease categories. What enzyme is deficient? What accumulates where? What clinical manifestations are present?

*Hepatic: deficient in glucose-6-phosphatase. Glycogen accumulates in hepatic cells and in kidney. Hypoglycemia, gout, high cholesterol. Myopathic: deficient in muscle phosphatase. No lactate ever accumulates in muscles. Intense pain when exercising. High CPK. Miscellaneous: deficient in alpha-glucosidase. Glycogen accumulates under sarcolemma membrane. Cardiac disease & cardiomegaly.


^LDL receptor mutations


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^How does the liver play a central role in cholesterol metabolism?


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^Trisomy 21 Clinical Presentations


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^Trisomy 18 Clinical Presentations


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^Trisomy 13 Clinical Presentations


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^Why do Klinefelter patients exhibit decreased masculinity?

*They have two X chromosomes. The X chromosome codes for the androgen receptor. Androgen response is amplified with shorter CAG repeats, but in Klinefelter's the X chromosome with shorter CAG repeats is inactivated.


^Klinefelter symptoms

*FSH is elevated, atrophied testis, gynecomastia, infertility and female hair distribution. These patients have 20x greater risk of breast cancer.


^Alkaptonuria (Ochronosis)

*Deficiency in homgenistic oxidase. Inability to metabolize Phe or Tyr. Ochronosis (black pigmenting) in collagen from excess homogenistic acid.


^Fragile X Syndrome

*Excessive trinucleotide repeats of G and C in the FMR gene coding for the FMR protein. Results in male retardation and huge balls. Gets worse with generations due to extension of trinucleotide repeats.


^How can mother and father genetic imprinting contribute to different diseases on chromosome 15?

*A paternal deletion of the gene results in Angelman Syndrome. A maternal deletion of the gene results in Prader-Willi Syndrome. Both syndromes result in slight variations in mental retardation.