Autosomal Dominant Inheritance

Question 1

mutations in one allele that can lead to structural change in protein that interferes with the function of the wild-type protein

Answer 1

dominant negative mutations

Question 2

example of a dominant negative mutation that has a mutation in collagen 1 alpa1 chain and has sx’s of BITE

Answer 2

osteogenesis imperfecta

Question 3

this is due to loss of function of fibrillin-1 (FBN1), making it unable to sequester TGF-beta

Answer 3

Marfan syndrome; dominant negative mutation

Question 4

in autosomal dominant inheritance, what is the chance of a child inheriting disorder

Answer 4

50%

Question 5

examples of incomplete dominance (2)

Answer 5

familial hypercholesterolemia

achondroplasia

Question 6

example of autosomal dominant mutation that leads to gain of function and TF sequestration

Answer 6

Huntington’s disease

Question 7

phenotypically normal family members do or do not transmit phenotype to children

Answer 7

do not transmit

Question 8

most common cause of dwarfism

Answer 8

achondroplasia

Question 9

rhizomelic shortening of arms and legs, macrocephaly and prominent forehead

Answer 9

achondroplasia

Question 10

caused by FGFR3 mutations

Answer 10

achondroplasia

Question 11

gain of function mutation that results in constitutive activation of FGFR3 and inhibition of chondrocyte proliferation

Answer 11

achondroplasia

Question 12

unaffected parents with affected child of achondroplasia would deal with what

Answer 12

gonadal mosaicism

Question 13

80% de novo mutations in paternal germline

Answer 13

achondroplasia

Question 14

caused by mutation in NF2 tumor suppressor gene

Answer 14

Neurofibromatosis 2

Question 15

bilateral vestibular schwannomas (benign tumors of nerve VIII) and meningiomas

Answer 15

neurofibromatosis 2

Question 16

patient presents with tinnitus, sensorineural hearing loss, and balance problems (think damage to CN VIII)

Answer 16

neurofibromatosis 2

Question 17

mutation in one allele is inherited, then a second mutation occurs in one cell that can lead to what

Answer 17

a tumor

Question 18

the two-hit hypothesis that leads to a tumor manifests as what kind of cancer

Answer 18

autosomal dominant

Question 19

deals with variable expressivity and locus heterogeneity at PKD1 and PKD2 loci

Answer 19

autosomal dominant polycystic kidney disease (ADPKD)

Question 20

one normal and one abnormal allele at particular locus, the loss of normal allele produces a locus with no normal function

Answer 20

loss of heterozygosity

Question 21

presentations of this disease include: progressive renal failure*
renal and hepatic cysts*
UTIs
hematuria
nocturia
flank pain
hypertension
end-stage renal disease by 60***

Answer 21

autosomal dominant polycystic kidney disease (ADPKD)

Question 22

caused by mutation in APC gene
(de novo gene mutations); autosomal dominant

Answer 22

familial adenomatous polyposis

Question 23

present in affected individual but absent from both biological parents’ genomes

Answer 23

de novo mutation

Question 24

leads to buildup of adenomatous polyps in colon; almost 100% form colonic tumors by 40 years (many poly[s unlike Lynch Syndrome)

Answer 24

familial adenomatous polyposis

Question 25

patients present with nonspecific sx’s like diarrhea, abdominal discomfort, or rectal bleeding

Answer 25

FAP

Question 26

can be spotted during physical exam with pigmented lesions of retina

Answer 26

FAP

Question 27

presents with telangiectasia in skin, mucous membranes, and some organs; predisposes to bleeding

Answer 27

hereditary hemorrhagic telangiectasia

Question 28

mutations in HHT1(ENG) and HHT2 (ACVRL1); malformations occur predominantly in lungs and brain

Answer 28

hereditary hemorrhagic telangiectasia

Question 29

most common cause of hereditary hemolytic anemia

Answer 29

hereditary spherocytosis

Question 30

presents with jaundice, fatigue, pallor, sphlenomegaly, iron overload

tx: remove spleen

Answer 30

hereditary spherocytosis

Question 31

mutations in spectrin, ankyrin, band 3 and protein 4.1; 75% autosomal dominant

Answer 31

hereditary spherocytosis

Question 32

tall stature
skeletal anomalies
dislocation of lens upwards
mitral valve prolapse
aortic dilatation
spontaneous pneumothorax

Answer 32

Marfan’s syndrome

Question 33

mutation in FBN1 gene

Answer 33

Marfan’s syndrome

Question 34

WT allele along with variant allele is insufficient to produce WT phenotype

Answer 34

haploinsufficiency

Question 35

marfan syndrome pain in back , legs, and abdomen diminish when patient is doing what

Answer 35

lying flat

Question 36

caused by mutation in MEN1 (a tumor suppressor)

Answer 36

multiple endocrine neoplasia type I

Question 37

deals with angiofibromas over nose and cheeks

MEN1: 3 P’s

Answer 37

multiple endocrine neoplasia type I

Question 38

the 3 P’s of multiple endocrine neoplasia type I

Answer 38

Pituitary
parathyroid
pancreatic

Question 39

another name for multiple endocrine neoplasia type I

Answer 39

Wermer syndrome

Question 40

another name for multiple endocrine neoplasia type II

Answer 40

Sipple syndrome

Question 41

caused by mutations in RET protooncogene

Answer 41

multiple endocrine neoplasia type II

Question 42

presents with medullary thyroid carcinoma, parathyroid hyperplasia, and pheochromocytoma

Answer 42

multiple endocrine neoplasia type II

Question 43

benign tumor that develops in adrenal gland

Answer 43

pheochromocytoma

Question 44

caused by mutations in TSC1 and TSC2 (tuberin mutations***)

Answer 44

tuberous sclerosis complex

Question 45

non-cancerous tumors
giant cell astrocytoma*
cortical tubers**
subependymal nodules

Answer 45

tuberous sclerosis complex

Question 46

along with the many benign tumors, patient can present with facial angiofibromas and “ash leaf spots”

Answer 46

tuberous sclerosis complex

Question 47

60-80% of TSC patients have benign tumors of what organ

Answer 47

kidneys

Question 48

in children with TSC, specific tumors, (rhabdomyomas) are found where

Answer 48

heart muscle

Question 49

caused by mutations in VHL gene;
characterized by visceral cysts and benign tumors

Answer 49

von Hippel-Lindau disease

Question 50

patient presents with problems with balance and vision problems-angiomatosis and high bp; PLEIOTROPY

Answer 50

von Hippel-Lindau disease