genetics

Question 1

unilateral cafe au lait spots, polyostotic fibrous dysplasia, precocious puberty, endocrine abnl?

Answer 1

McCune Albright

survivable if pt has mosaicism

Question 2

what is locus heterogeneity? what’s an example?

Answer 2

mutations at different loci produce a similar phenotype

e.g. albinism

Question 3

what is allelic heterogeneity? what’s an example?

Answer 3

different mutations in the same locus produce the same phenotype
e.g. b-thalassemia

Question 4

vitamin-D resistant rickets?

Answer 4

hypophosphatemic Rickets

phosphate wasting at proximal tubule

Question 5

myopathy, lactic acidosis, CNS dz, ragged red fibers on biopsy?

Answer 5

mitochondrial myopathies

failure in OXPHOS

Question 6

B/L massive enlgmt of kidneys due to cysts?

Answer 6

ADPKD

• 85% PKD1 mtn (chrom 16)
• 15% PKD2 mtn (chrom 4)

Question 7

FAP gene?

Answer 7

APC gene on chromosome 5 (5 letters in polyp)

Question 8

branching skin lesions, recurrent epistaxis, skin discoloration, AVMs, GI bleeds, hematuria?

Answer 8

hereditary hemorrhagic telangiectasia.

AD

Question 9

chromosome for huntington’s dz?

Answer 9

4 (hunting 4 food)

Question 10

tall and long, pectus excavatum, hypermobile joints, arachnodactyly, upward lens subluxation, aortic aneurysm/dissection?

Answer 10

Marfan - AD

FBN1 gene, chromosome 15 –> fibrillin

Question 11

cafe au lait, cutaneous neurofibromas, optic gliomas, pheos, iris hamartomas?

Answer 11

NF1 - AD

NF1 gene, chromosome 17 (17 letters in von Recklinghausen)

Question 12

bilateral acoustic schwannomas, cataracts, meningiomas?

Answer 12

NF2 - AD

NF2 gene on chromosome 22

Question 13

Von Hippel Lindau?

Answer 13

development of numerous benign/malignant tumors

assoc with VHL gene deletion on chromosome 3

Question 14

gene of CF?

Answer 14

AR
CFTR on chrom 7
usually phe508 deletion

Question 15

CF pathophys?

Answer 15

Cl channel: secretes in lungs and GI, absorbs in sweat
mutation –> misfolded –> not in membrane –> decreased Cl secretion and compensatory increase in Na and H2O reabsorption

Question 16

dx of CF?

Answer 16

Cl > 60mEq/L in sweat

increased immunoreactive trypsinogen in newborn screen

Question 17

complications of CF?

Answer 17

recurrent pulm infx, bronchiectasis, bronchitis
panc insufficiency
malabsorption
meconium ileus
infertility (M) /subfertility (F)
ADEK deficiencies

Question 18

tx of CF?

Answer 18

NAC –> loosen mucus plugs

dornase alfa –> clear leukocytic debris

Question 19

calf pseudohypertrophy, Gower maneuver, waddling?

Answer 19

DMD, XL
frameshift in DMD gene –> dystrophin protein truncation
dx: Western blot and mm biopsy

** MCC of death = dilated cardiomyopathy

Question 20

less severe Duchenne?

Answer 20

Becker, XL

non-frameshift insertions - dystrophin is partially functional

Question 21

myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia?

Answer 21

myotonic dystrophy type I, AD
CTG expansion in DMPK gene –> abnl expression of myotonin protein kinase

My Tonia, My Testicles, My Toupee, My Ticker

Question 22

post-pubertal macroorchidism, long face, large ears, autism, MVP?

Answer 22

Fragile X, XL

CGG expansion in FMR1 gene

Question 23

1st tri screen in Downs vs Edwards vs Patau?

Answer 23

Downs: dec PAPP-A, inc HCG, increased nuchal translucency
Edwards: dec PAPP-A, dec HCG
Patau: dec PAPP-A, dec HCG, inc nuchal translucency

Question 24

Robertsonian translocation - chromosomes most commonly involved?

Answer 24

13
14
15
21
22

Question 25

cri du chat?

Answer 25

microdeletion of 5p

Question 26

elfin facies, intellectual disability, hypercalcemia (increased vit D sensitivity), friendly with strangers, CV problems?

Answer 26

Williams

microdeletion of 7q (includes elastin)