Patterns of inheritance:
1. Type of inheritance pattern in familial hypercholesterolemia, Huntington’s,
Neurofibromatosis, and Marfans?
a. AD = affects structural genes usually
b. Familial hypercholesterolemia = ↑ LDL and absent LDL receptors
i. Severe atherosclerotic disease with corneal arcus and tendon xanthomas
c. Huntington disease:
i. Symptoms = depression, early onset dementia, choreiform movements,
caudate atrophy
ii. d/t trinucleotide repeats of CAG in chromosome 4
d. NF type 1:
i. Symptoms = café au lait spots, cutaneous neurofibromas, optic gliomas,
pheochromocytomas, lisch nodules
ii. 100% penetrance
e. NF type 2:
i. Chromosome 22
ii. Symptoms = B/L acoustic schwannomas, juvenile cataracts, meningiomas
and ependymomas
2. Describe AD inheritance.
a. Affected individuals have an affected parent
b. Either sex is affected
c. Variable to late onset usually
3. PKD: what mode of inheritance and what mutations?
a. AD
b. Chromosome 16 = PKD 1
c. Chromosome 4 = PKD 2
4. FAP: mode of inheritance and mutations?
a. AD
b. 5q APC gene
5. Hereditary spherocytosis: mode of inheritance and deficiency in what?
a. AD
b. Spectrin/Ankyrin deficiency causing hemolytic anemia
6. Li Fraumeni: mode of inheritance and gene defect?
a. AD
b. TSG p53 multiple malignancies: sarcoma, breast, leukemia, adrenal gland
7. Marfan syndrome: mode of inheritance and defect in what protein and gene?
a. AD
b. FBN1 (fibrillin) on chromosome 15 defective elastin binding
8. MEN syndromes associated with what and what mode of inheritance?
a. AD
b. Tumors of endocrine system (pancreas, parathyroid, pituitary, thyroid, adrenal
medulla)
9. Tuberous sclerosis: mode of inheritance?
a. AD
b. Incomplete penetrance + variable expression
c. Symptoms = “HAMARTOMAS”
10. VHL: mode of inheritance and defect?
a. AD
b. TSG VHL gene deletion on Chromosome 3
c. Numerous benign and malignant tumors
11. Type of inheritance pattern in Sickle cell, CF, PKU, and Kartegener’s?
a. AR = affects genes encoding for enzymes usually
12. Describe AR inheritance.
a. Unaffected parents
b. Either sex affected
c. Early/uniform onset
d. Often catalytic proteins
e. Sometimes occurs in consanguinity (incest)
13. What do fragile X and hypophosphatemic rickets (vit D resistant rickets) have in
common?
a. Both are XD!
14. XD inheritance:
a. Males cannot pass onto sons
b. Mothers transmit to 50% of offspring
c. Fathers to ALL daughters
15. Type of inheritance in Duchenne, G6PD def, Lesch-Nyhan, Ornithine transcarbamylase
def, Hemophilia A/B?
a. XR‼
16. What is a sign of mitochondrial inheritance?
a. Transmitted though mothers
b. Variable expression
c. Mitochondrial myopathies = ragged red fibers on muscle biopsy
17. Define codominance:
a. Both alleles contribute to phenotype
b. Ex: blood groups: A, B, AB; α1 antitrypsin deficiency
18. What is variable expressivity?
a. Disease may present differently in different individuals
b. Ex: NF type 1
19. What is incomplete penetrance?
a. Mutant genotype may not produce a mutant phenotype
b. Ex: BRCA 1 gene for breast cancer ↑ chances of getting breast cancer to 60%
(not 100%)
Trisomy disorders: