biochem: genetics

Question 1

hypophosphatemic rickets

Answer 1

vit-D resistant. X-linked dominant. incr. phosphate wasting at proximal tubule

Question 2

mitochondrial myopathies

Answer 2

rare, present w/myopathy, lactic acidosis, and CNS dz. caused by failure of oxidative phosphorylation. muscle Bx shows “ragged red fibers”

Question 3

polycystic kidney dz

Answer 3

autosomal dominant. b/l massive enlargement of kidneys due to multiple large cysts. 85% due to PKD1 mutation on chromosome 16

Question 4

familial adenomatous polyposis

Answer 4

autosomal dominant. colon becomes covered w/adenomatous polyps after puberty. progresses to CA unless colon is resected. mutations on chromosome 5q

Question 5

familial hypercholesterolemia

Answer 5

autosomal dominant. defective/absent LDL receptor -> elevated LDL -> severe atherosclerosis, corneal arcus, tendon xanthomas

Question 6

hereditary hemorrhagic telangiectasia

Answer 6

autosomal dominant. inherited disorder of blood vessels -> branching skin lesions, recurrent epistaxis, skin discolorations, AVMs, GI bleeding, hematuria

Question 7

hereditary spherocytosis

Answer 7

autosomal dominant. spheroid erythrocytes due to spectrin or akyrin defect; hemolytic anemia; inc. MCHC, inc. RDW. Tx: splenectomy

Question 8

HD

Answer 8

autosomal dominant. -> depression, progressive dementia, choreiform movements, and caudate atrophy. inc. DA, dec. GABA, dec. ACh in the brain. gene on chr. 4 - trinucleotide repeat d/o (CAG). demonstrates anticipation: more repeats -> younger age of onset

Question 9

li-fraumeni syndrome

Answer 9

autosomal dominant. abnormalities in TP53 -> multiple malignancies at young age. sarcoma, breast, leukemia, adrenal gland.

Question 10

marfan syndrome

Answer 10

autosomal dominant. FBN1 gene mutation on chromosome 15 -> defective fibrin (scaffold for elastin) -> connective tissue d/o. lens subluxation is typically upward

Question 11

MEN

Answer 11

autosomal dominant. familial tumors of endocrine glands (pancreas, parathyroid, pituitary, thyroid, and adrenal medulla). MEN 1 - MEN1 gene. MEN 2 - RET gene

Question 12

NF1

Answer 12

autosomal dominant. neurocutaneous d/o - cafe au lait spots, cutaneous neurofibromas, optic gliomas, pheochromocytomas, lisch nodules (pigmented iris hamartomas). 100% penetrance, variable expression. caused by NF1 mutation on chr. 17

Question 13

NF2

Answer 13

autosomal dominant. b/l acoustic schwannomas, juvenile cataracts, meningiomas, and ependymomas. NF2 mutation on chr. 22 (NF2=chr22)

Question 14

tuberous sclerosis

Answer 14

autosomal dominant. neurocutaneous d/o w/multi-organ involvement. numerous benign hamartomas. incomplete penetrance, variable expression

Question 15

von hippel-lindau dz

Answer 15

autosomal dominant. development of many benign and malignant tumors. deletion of VHL tumor suppressor gene on chromosome 3p (3 word name)

Question 16

autosomal recessive dzs

Answer 16

albinism, PKD, CF, glycogen storage dzs, hemochromatosis, kartageners, mucopolysaccharidoses (except hunter), phenylketonuria, SS anemia, sphingolipidoses (except fabry), thalassemias, wilson dz

Question 17

CF mutations

Answer 17

typically CFTR on chr. 7. commonly Phe508.

Question 18

CFTR encodes

Answer 18

ATP-gates Cl channels, secreting Cl in lungs and GI, reabsorbing Cl in sweat glands -> abnormally thick mucus

Question 19

CF Dx

Answer 19

inc. [Cl] (>60mEq/L) in sweat. Can present with contraction alkalosis and hypokalemia (like loop diuretic). inc. immunoreactive trypsinogen on newborn screen.

Question 20

CF complications

Answer 20

lung infections (pseudomonas), chronic bronchitis, bronchiectasis, reticulonodular pattern on CXR, pancreatic insufficiency, malabsorption w/steatorrhea and nasal polyps. meconium ileus in newborns. infertility in males. fat-soluble vit deficiencies (ADEK)

Question 21

CF Tx

Answer 21

N-acetylcysteine to loosen mucus plugs (cleaves disulfide bonds w/in mucus glycoproteins), dornase alfa (DNAse) to clear leukocytic debris

Question 22

X-linked recessive d/os mnemonic

Answer 22

Be Wise, Fool’s GOLD Heeds Silly HOpe: Bruton agammaglobulinemia, Wiskott-aldrich syndrome, Fabry dz, G6PD, Ocular albinism, Lesch-nyhan syndrome, Duchenne (and becker) muscular dystrophy, Hunter Syndrome, Hemophilia A and B, Ornithine transcarbamylase deficiency

Question 23

Duchenne muscular dystrophy

Answer 23

Duchenne = deleted dystrophin. x-linked frameshift mutation -> truncated dystrophin -> inhibited muscle regeneration. Begins in pelvic girdle, progresses superiorly. Pseudohypertrophy of calf muscles due to fibrofatty replacement. Gower maneuver, waddling gait. Onset before 5. Die of dilated cardiomyopathy

Question 24

Becker muscular dystrophy

Answer 24

x-linked non-frameshift insertions in dystrophin gene -> partially fxnal protein -> less severe, later onset.

Question 25

myotonic type 1 muscular dystrophy

Answer 25

autosomal dominant. CTG trinucleotide repeat expansion in DMPK gene -> abnormal expression of myotonin protein kinase -> myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia. My Tonia, My Testicles, My Toupee, My Ticker

Question 26

Fragile X syndrome

Answer 26

x-linked defect affecting methylation and expression of FMR1 gene = 2nd most common cause of genetic intellectual disability. Post-pubertal macroorchidism, long face w/large jaw, large everted ears, autism, miral valve prolapse

Question 27

trinucleotide repeat expansion dzs mnemonic

Answer 27

Try hunting for my fried eggs: Huntington’s, myotonic dystrophy, friedreich ataxia, fragile X. or X-Girlfriend’s First Aid Helped Ace My Test.

Question 28

chr. 3 d/o

Answer 28

von hippel-lindau, renal cell carcinoma

Question 29

chr. 4 d/o

Answer 29

ADPKD w/PKD2 defect, HD

Question 30

chr. 5 d/o

Answer 30

cri-du-chat syndrome, familial adenomatous polyposis

Question 31

chr. 7 d/o

Answer 31

williams syndrome, CF

Question 32

chr. 9 d/o

Answer 32

friedreich ataxia

Question 33

chr. 11 d/o

Answer 33

wilms tumor

Question 34

chr. 13 d/o

Answer 34

patau syndrome, wilson dz

Question 35

chr. 15 d/o

Answer 35

parader-willi, angelman syndrome

Question 36

chr. 16 d/o

Answer 36

ADPKD w/PKD1 defect

Question 37

chr. 17 d/o

Answer 37

NF1

Question 38

chr. 18 d/o

Answer 38

edwards syndrome

Question 39

chr. 21 d/o

Answer 39

down syndrome

Question 40

chr. 22

Answer 40

NS2, digeorge syndrome (22q11)

Question 41

chr. X d/o

Answer 41

fragile X, X-linked agammaglobinemia, klinefelter

Question 42

robertsonian translocation

Answer 42

long arms of 2 acrocentric chromosomes fuse at the centromere and 2 short arms are lost. balanced translocations -> normal phenotype. unbalanced translocations -> miscarriage, stillbirth, chromosomal imbalance

Question 43

cri-du-chat syndrome

Answer 43

congenital microdeletion of 5p -> microcephaly, intellectual disability, high-pitched crying, epicanthal folds, VSD

Question 44

williams syndrome

Answer 44

congenital microdeletion of 7q (including elastin). -> elfin facies, intellectual disability, hypercalcemia (inc. vit. D sensitivity), good verbal skills, extreme friendliness, CV problems

Question 45

CATCH-22 syndrome

Answer 45

microdeletion of 22q11 -> variable: cleft palate, abnormal facies, thymic aplasia (-> T cell deficiency), hypocalcemia (2/2 parathyroid aplasia). digeorge: thymic, parathyroid, and cardiac. velocardiofacial: palate, facial, and cardiac