Genetics - Cole

Question 1

Etiology of Hirschsprung disease

Answer 1

abnormal neural growth, migration, and differentiation

Question 2

Short segment form of Hirschsprung disease

Answer 2

does not extend beyond upper sigmoid

Question 3

Long segment form of Hirschsprung disease

Answer 3

extends proximal to sigmoid

Question 4

Clinical presentation of Hirschsprung disease

Answer 4

megacolon, lack of colon peritalsis

Question 5

What other syndrome is commonly associated with Hirschsprung disease

Answer 5

Down syndrome

Question 6

Who is Hirschsprung disease most common in (incidence)

Answer 6

male and asians

Question 7

Most common gene associated with Hirschsprung disease

Answer 7

RET gene

Question 8

Mode of inheritance for Hirschsprung disease in RET gene

Answer 8

Autosomal dominant

Question 9

Protein function involved in Hirschsprung disease and RET gene

Answer 9

tyrosine kinase receptor

Question 10

Proto-oncogene

Answer 10

genes that code for proteins that help regulate cell growth

Question 11

what cell is RET gene expressed in

Answer 11

neural crest cells

Question 12

Hirschsprung is what kind of mutation

Answer 12

Loss-of-function

Question 13

Loss-of-function mutation

Answer 13

reduced or abolished protein function

Question 14

What syndrome is associated with gain-of-function mutation

Answer 14

MEN (multiple endocrine neoplasia) syndrome

Question 15

Gain-of-function

Answer 15

type of mutation in which altered gene product has new function or new pattern of expression

Question 16

Function of RET gene

Answer 16

gives instructions to proteins that are involved in signaling within cells

Question 17

RET and Hirschsprung disease association

Answer 17

result in nonfunctional RET protein

Question 18

Result of no RET protein signaling

Answer 18

enteric nerves do not develop

Question 19

Hemochromatosis

Answer 19

liver disorder

Question 20

Etiology of hemochromatosis

Answer 20

Decrease in HFE function

Question 21

Function of AAT

Answer 21

protect the cell from elastase overactivation`

Question 22

2 diseases/syndromes associated with hemochromatosis

Answer 22

Wilson disease and Menkes syndrome

Question 23

Secondary hemochromatosis

Answer 23

not genetically related- but due to build-up of iron from anemia, liver disease, or alcoholism

Question 24

Iron overload through too much absorbed

Answer 24

iron is excess of transferrin capacity

Question 25

Where does iron excess deposit in the body

Answer 25

liver, heart, and endocrine organs

Question 26

What can iron excess in body lead to

Answer 26

tissue damage and fibrosis of liver, heart, and endocrine organs

Question 27

Iron overload through too many erythrocytes destroyed

Answer 27

accumulates in macrophages first then tissue parenchyma

Question 28

Most common gene associated to iron absorption regulation

Answer 28

HFE

Question 29

Mode of inheritance for HFE gene

Answer 29

autosomal recessive

Question 30

Factors that decrease iron absorption

Answer 30

regular blood transfusions, high iron diet, iron loading vitamins

Question 31

Factors that increase iron absorption

Answer 31

celiac disease, pica, GI bleeding

Question 32

HFE function

Answer 32

regulate circulating iron uptake by regulating transferrin receptor (TFR1/2) and transferrin

Question 33

Hepcidin

Answer 33

regulator of entry of iron into circulation

Question 34

Transferrin

Answer 34

iron-binding blood plasma glycoprotein that controls level of free iron

Question 35

Ferroportin

Answer 35

transmembrane protein that transports iron from inside cell to outside cell

Question 36

What inhibits ferroportin

Answer 36

hepcidin

Question 37

T/F hemochromatosis is common in young infants

Answer 37

F- late onset, 40-50 males and later onset in females

Question 38

S/S of hemochromatosis

Answer 38

increased pigmentation, fatigue, hepatospenomegaly

Question 39

Endocrine organs affected by hemochromatosis

Answer 39

diabetes (pancreas), hypopituitarism (pit), hypogonadism (gonad), hypoparathyroidism (thyroid)

Question 40

Skin color of person with hemochromatosis

Answer 40

bronze skin

Question 41

ONLY sign or symptom specific to hemochromatosis

Answer 41

"The Iron Fist"

Question 42

Treatment for hemochromatosis

Answer 42

therapeutic phlebotomy to remove iron in blood

Question 43

Hereditary hemochromatosis gene

Answer 43

C282Y - cys to tyr mutation

Question 44

Incidence of hemochromatosis

Answer 44

Northern European ancestry

Question 45

Two genes involved in copper homeostasis

Answer 45

ATP7A and ATP78

Question 46

Ceruloplasmin

Answer 46

major copper-carrying protein in the blood and iron metabolism

Question 47

Regulation of iron absorption by ceruloplasmin

Answer 47

ceruloplasmin promotes iron loading onto transferring with only binds Fe2+ --> reduced Cu2+ transports Fe2+ to increase Fe2+ absorption

Question 48

Gene associated with Menkes Syndrome

Answer 48

ATP7A

Question 49

If ATP7A is mutated

Answer 49

Menkes Syndrome- uptake of copper impaired and copper deficiency occurs

Question 50

Clinical presentation of Menkes

Answer 50

infant healthy until 2-3 months, loss of developmental milestones, hypotonia, and failure to thrive

Question 51

MAIN sign of Menkes

Answer 51

kinky hair, short, sparse, lightly pigmented

Question 52

Vessels of Menkes patient

Answer 52

very tortuous blood vessels

Question 53

Gene associated with Wilson disease

Answer 53

ATP7B

Question 54

ATP7B mutations for Wilsons disease

Answer 54

prevent release of Cu2+ from hepatocytes causing decreased ceruloplasmin levels and Fe2+ and Fe3+ affected

Question 55

S/S of Wilsons Disease

Answer 55

progressive lenticular degeneration, softening of lenticular nucleus, liver cirrhosis

Question 56

Clinical presentation of Wilsons Disease

Answer 56

movement disorders, rigid dystonia, Kayser-Fleischer ring

Question 57

Kayser-Fleischer ring

Answer 57

copper deposition in Descemet's membrane of cornea

Question 58

Copper levels in liver of Menkes syndrome

Answer 58

decreased

Question 59

Copper levels in liver of Wilsons

Answer 59

increased

Question 60

Serum copper in Menkes and Wilsons

Answer 60

decreased

Question 61

Treatment for Menkes

Answer 61

daily copper/histidine injections

Question 62

Treatment for Wilsons

Answer 62

copper chelation