Dominant Diseases

Question 1

IN almost all AD disoders, how will it present clinically?

Answer 1

significantly

Question 2

are most pts with dominant inherited diseases heter or homozygous

Answer 2

heterozygous

Question 3

homozygotes are almost always affected more ____ than heterozygotes with AD

Answer 3

severely

Question 4

what are the 3 mechanisms for AD occur

Answer 4

1. haploinsufficiency
2. gain of function mutations
3. dominant negative mutations

Question 5

Define haploinsufficienty

Answer 5

expression from one copy of gene is not adquate to meet physiological requirements and produce a normal phenotype
Half is not enough!

Question 6

mutations in haploinsufficiency always have what result

Answer 6

loss of function

Question 7

what types of mutations can cause loss of function

Answer 7

almost all: missense, nonsesne, splice, framshift, deletion, insertoin, translocation

Question 8

What are some examples of haploinsuficiency

Answer 8

TFs
prophyria’s
marfan syndrome, Type I osteogenesis imperfecta

Question 9

What does NPS stand for?

Answer 9

Nail Patella syndrome

Question 10

Where is the mutation in NPS

Answer 10

Lmx1b

Question 11

What does LMX1B gene encode

Answer 11

Lmx1b transcription factor

Question 12

what does Lmx1b transcription factor play a role in

Answer 12

dorso-ventral patterinning of limbs

Question 13

what is pleitropy

Answer 13

clinical presentation affects a lot of seemingly unrelated organ systems

Question 14

what disease has nail dysplasia, absent/hypoplastic patellae, elbow dysplasia, pterygia, extoses of the ilia, contractures and hyperextensibility of interphalgneal joints, kidney disease/failure, glaucoma

Answer 14

NPS

Question 15

what is penetrance

Answer 15

probably that an individual will present with a phenotype given a certain genotype (the probability they will actually present)

Question 16

What kind of penetrance does NPS have

Answer 16

complete - 100% will have phenotype

Question 17

what is variable expressitivity

Answer 17

individuals carrying the same mutation may present with different phenotypes

Question 18

does NPS have variable expressivity?

Answer 18

yes

Question 19

why does variable expressivity occur

Answer 19

variation of other genes like modifier genes

stochastic events in development (random chance)

Question 20

variable expressivity is not caused by what

Answer 20

allelic heterogenieity

Question 21

all mutations that lead to NPS result in what

Answer 21

loss of function resulting in haploinsufficiency

Question 22

Cleidocranial dysplasia has a mutation where?

Answer 22

Runx2

Question 23

What is MOI for Cleidocranial dysplasia?

Answer 23

AD

Question 24

Mutations in TF often cause a range of what

Answer 24

clinical features

Question 25

why do mutations in TF often cause of a range of clinical features

Answer 25

b/c the same factor is used in different cell types at different stages in developement

Question 26

how do most TF mutations act

Answer 26

most via haploinsuffiency

Question 27

What defect is prophyrias

Answer 27

enzyme defects (enzymopathies of heme biosynthesis)

Question 28

what is exception of enzymopathies being AR

Answer 28

prophyrias

Question 29

acute attacks of vomiting & pain, neurological/psychiatric problems, cardiovascular symtpoms is what disease

Answer 29

acute hepatic porphyrias

Question 30

What does AIP stand for

Answer 30

acute intermittent porphyrai

Question 31

What is the major acute hepatic porphyria?

Answer 31

AIP