Gain of Function Mutation

Question 1

What is a gain of function mutation

Answer 1

increased or novel gene function

Question 2

What type of mutation causes gain of function

Answer 2

missense, gene duplciations, chromosomal translocations

Question 3

What is main disease when FGFR3 is mutated

Answer 3

achondroplasia

Question 4

What does FGFR3 encode?

Answer 4

tyrosine kinase receptor

Question 5

What does TD stand for

Answer 5

Thanatophoric Dysplasia

Question 6

What is mode of inheritance of TD

Answer 6

AD

Question 7

Do pts with TD usually survive?

Answer 7

usually still born

Question 8

what mutation is thanatophoric dysplasia caused by

Answer 8

sporadic mutatins

Question 9

Death in uterio or perinatal lethal, limb shortening, severe frontal bossing, very small chest, death due to respiratory failure is what disease

Answer 9

Thanatophoric Dysplasia

Question 10

What is the main type of Thanatorphic Dysplasia

Answer 10

TD1

Question 11

What is the most common form of swarfism

Answer 11

Achondroplasia

Question 12

What are most mutations caused by that cause achondroplasia

Answer 12

sporadic mutation

Question 13

What is the specific mutation that causes achondroplasia

Answer 13

G380R

Question 14

If pt has short stature, shortening of long bones of limbs, large head, low nasal bridge, lumbar lordosis, normal life expectancy & intelligence is what disease?

Answer 14

achondroplasia

Question 15

What is a major life threatening complication that can occur with pts in achondroplasia

Answer 15

compression of foramen magnum

Question 16

When does homozygous achondroplasia occur

Answer 16

when two people with achondroplasia mate

Question 17

what is the phenotype of homozygous achondroplasia

Answer 17

perinatal lethal (comparable to TD1)

Question 18

What test could be done to confirm if pt has homozygous achondroplasia and TD1?

Answer 18

Look at parents - if both parents have achondroplasia then pts is homozygous achondroplasia

Question 19

What is the biggest role in FGFR3 regarding development

Answer 19

bone growth

Question 20

What is biggest role in FGFR2 regarding development

Answer 20

skull

Question 21

What is disease when FGFR2 is mutated?

Answer 21

Apert syndrome

Question 22

gain of function and loss of function mutations will have what kind of phenotypes compared to each other

Answer 22

opposite

Question 23

WHat is FGFR3’s role in chondrocyte proliferation

Answer 23

it stops proliferation so it slows bone growth

Question 24

Gain of function mutations do what to dimerization of RTKs

Answer 24

they increase dimerization

Question 25

A loss of function mutation has what kind of phenotype compared to achondroplasia

Answer 25

opposite

Question 26

Explain the knockout of FGFR3 and knock in of FGFR3

Answer 26

knockout: longer growth of limbs | knock in: shorter limbs, smaller skeletons

Question 27

What does CATSHLS stand for

Answer 27

camptodactylyl tall stature, and hearing loss syndrome

Question 28

what human disease has loss of function in FGFR3?

Answer 28

CATSHLS

Question 29

clinical presentatuion: tall stature, severe lateral tibial deviation, scoliosis, compacdyctyal is what disease

Answer 29

CATSHLS

Question 30

What does FOP stand for

Answer 30

fibrodysplasia ossificans progressiva

Question 31

FOP is caused by mutations in what gene

Answer 31

ACVR1

Question 32

What is ACVR1?

Answer 32

BMP receptor part of TGF beta family

Question 33

clinical presentation: heterotropic ossification of skeletal muscles, tendons, ligaments and fascia, congenital malformation of big toes is what disase

Answer 33

FOP

Question 34

clinical presentation: heterotropic ossification of skeletal muscles, tendons, ligaments and fascia, congenital malformation of big toes is what disase

Answer 34

FOP

Question 35

What kind of mutation is in ACVR1?

Answer 35

gain of function

Question 36

What does BMP stand for?

Answer 36

Bone Morphogenetic proetins

Question 37

What do BMPs do?

Answer 37

induce bone and cartilage formation

Question 38

Gain of function mutations in BMP receptor leads to what

Answer 38

heterotrophic ossification

Question 39

What is the BMP receptor

Answer 39

ACVR1