Pathology: Genetics

Question 1

Autosomal

Answer 1

*Any chromosomal disorder not on the sex genes.

Question 2

^Genetic heterogeneity

Answer 2

*Single phenotype caused by any number of genetic variations

Question 3

^Why are enzymatic mutations more impacted by recessive genes?

Answer 3

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

Question 4

^Why are regulatory systems more prone to dominant genes?

Answer 4

*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.

Question 5

^Polygenic diseases

Answer 5

*Many genes contribute to the overall condition of disease.

Question 6

^Clinical presentations of Turner’s Syndrome

Answer 6

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

Question 7

^Thallacemia

Answer 7

*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.

Question 8

^Thallacemia Clinical Symptoms

Answer 8

*Anemia due to decreased Hgb function.

Question 9

Answer 9

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

Question 10

Answer 10

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

Question 11

^Why is Autosomal Polycystic Kidney Disease dominant?

Answer 11

*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.

Question 12

^What condition is related to development of berry aneurisms?

Answer 12

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

Question 13

Answer 13

*Autosomal Polycystic Kidney Disease.

Question 14

^Hurler’s Syndrome Enzyme Deficiency

Answer 14

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

Question 15

^How is accumulation of mucopolysaccharides pleiotropic?

Answer 15

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

Question 16

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

Answer 16

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

Question 17

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

Answer 17

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

Question 18

^Clinical features of mucopolysaccharidosis.

Answer 18

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

Question 19

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

Answer 19

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

Question 20

^Tay-Sachs clinical manifestations

Answer 20

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

Question 21

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

Answer 21

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

Question 22

^Niemann-Pick A & B clinical manifestations

Answer 22

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

Question 23

^Niemann-Pick C mutation, accumulate and symptoms

Answer 23

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

Question 24

^Gaucher enzyme deficiency, accumulate and target tissue

Answer 24

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

Question 25

^Gaucher clinical manifestations

Answer 25

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

Question 26

Answer 26

*Alcian blue stain of mucopolysaccharides.

Question 27

Answer 27

*Cytoplasmic clearing typical of lysosomal storage disorders.

Question 28

Answer 28

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

Question 29

^How is hypercholesterolemia developed genetically?

Answer 29

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

Question 30

Answer 30

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

Question 31

Answer 31

Xanthoma. Cholesterol accumulation under the skin.

Question 32

^Down’s Syndrome Clinical Manifestations

Answer 32

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

Question 33

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

Answer 33

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

Question 34

^How does intracellular cholesterol affect the cell?

Answer 34

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

Question 35

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

Answer 35

*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.

Question 36

^LDL receptor mutations

Answer 36

*

Question 37

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

Answer 37

*

Question 38

^Trisomy 21 Clinical Presentations

Answer 38

*

Question 39

^Trisomy 18 Clinical Presentations

Answer 39

*

Question 40

^Trisomy 13 Clinical Presentations

Answer 40

*

Question 41

^Why do Klinefelter patients exhibit decreased masculinity?

Answer 41

*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.

Question 42

^Klinefelter symptoms

Answer 42

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

Question 43

^Alkaptonuria (Ochronosis)

Answer 43

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

Question 44

^Fragile X Syndrome

Answer 44

*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.

Question 45

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

Answer 45

*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.