Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pathology 2 > 1.2 Autosomal Dominant > Flashcards

1.2 Autosomal Dominant Flashcards

1
Q

Autosomal Dominant mutations

A

usually affects structural proteins or ones with complex functions –> making more wont help (rate limiting proteins), not single enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

AD with toxic abnormal gene product

A

gain of function – Huntington disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

AD with abromal product that interferes with other normal proteins

A

dominant negative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What autosomal dominant conditions is associated with young athletes that die?

A

Hypertrophic Cardiomyopathy – freq of 1/500 so it would be beneficial to screen for this and prevent fatality

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Familial Hyercholesteremia

A

AD disease where there is structural alteration in LDL receptor—-remember that this is the name of this specific disease bc there are other hypercholesterolemias that are familial but are not this!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is the most frequent mandelian disorder

A

familial hypercholesteremia – 1:500 heterozygous for FH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

where is the gene located for familial hypercholesterolemia

A

chromosome 19 and it is an extremely large gene so it_s a big gene target

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

identified mutations in familial hypercholesterolemia

A

900 identified – alterations include failure to synthesize receptor, inability to bind LDL, inability to internalize receptor, inability to disassociate LDL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

in FH there is inc in cholesterol bc

A

of dec in clearance and dec in feed back mechanisms stimulating inc synthesis of cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How does FH work wrt the liver

A

the LDL receptors on the liver don’t exist so the LDL that is present is not getting into the liver cell, so now the liver cell thinks there is low cholesterol and starts to synthesize more cholesterol. Normally that LDL getting into the cell via the receptor is going to inhibit HMG-coA reductase so there will be inhibition of synthesis bc the cell is like –hey we’ve got cholesterol stop making more.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

clearance of cholesterol

A

only if the LDL receptor exists on the liver cell can it get in and then be put into VLDL that are then cleared by lypolysis in circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Clinical course of heterozygous FH

A

2-3 fold inc in serum cholestorol, inc rates of ACVD. See xanthomas on eyelids and flexor tendons – serum will be milky white

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

clinical course of homozygous FN

A

massive inc in serum cholesterol, can have MI in teens or <30yo — serum will be milky white bc of all the excess fat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

grey around iris

A

high cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

statins in normal ppl

A

don_t really lower cholesterol but they do have a lower rate of heart attack and it is thougt that statins also have antiinflammatory capacity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Marfan syndrome

A

autosomal dominant – generalized elastic tissue defect –>hyperflexible joints, aortic aneurysms, mitral valve prolapse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Even though Marfan’s syndrom is a generalized elastic tissue defect, it is not a mutation in elastin. Instead

A

Fibrilin -1 is the gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

fibrilin 1 mutations in Marfan’s

A

> 500 mutations mostly missense, mutations in fibrillin-1 gene–> have abnormal protein that impairs microfibril assembly; microfibrils are scaffold for elastic fibers–>DOMINANT NEGATIVE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

de novo/sporadic cases of disease

A

are mostly seen in AD diseases but not AR diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

sporadic cases of Marfan’s

A

03-Jan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what outcome does Marfan’s have on young athletes

A

sudden death

22
Q

characteristic features of Marfans

A

tall, thin, and long extremities, fingers, and toes; height unbalanced and contributed by long legs; hyper flexible joints; dilichocephalic with prominent supraorbital ridges (Abraham Lincolm); Dislocation of lenses (ectopia lentis). Rare and practically diagnostic; Mitral valve prolapse; dialation of aortic ring; Aortic insufficiency; Dissecting aneurysms(called aortic aneurysms now); variable expression (different mutations); major involvement in 2 of 4 organ systems and minor of 1 (skeletal, cardiovascular, skin, ocular)

23
Q

Aortic dissections in Marfan’s

A

get an intimal tear. Aorta has natural dissection planes bc there is so much longitudinal and circular muscle. When you have a tear, blood leaks out pushes inward

24
Q

Causes of sudden death

A

heart attack, stroke, ruptured saccular aneurysm, dissecting aneyrysm

25
Q

Elastic tissue in Marfan’s

A

cystic medial necrosis degeneration

26
Q

cause of dissecting aneurysms

A

distorted anatomy

27
Q

Aortic ring and Marfan’s

A

with elastic tissue defect and pressure defect, the aortic ring dialates. Aorta is retroperitoneal, tied down by parietal pleural. When you get to the arch it is mobile. Everytime you beat the arch moves. The dialation causes it to twist and with each beat it twists and wrinkles the intema and the anatomy is set up for a little tweak and tear leading to aortic dissection

28
Q

Most common cause of aortic dissection

A

hypertension — the question would have to give you much more information if you wanted to say the aortic dissection was due to marfan’s

29
Q

what happens to the heart when compressed

A

it stops beating

30
Q

double barrel aorta

A

sometimes (rarely) the dissection occurs inward and the wall gets thicker and endothelialized creating a double barrel aorta

31
Q

how does a mutation in fibrilin -1 cause long bone overgrowth?

A

certain things that induce bone growth are sequestered by fibrilin-1 and if you don’t have it, those things that are no longer sequestered will induce bone overgrowth

32
Q

Fibrilin 1 sequesters

A

TGF beta and reduces its availability

33
Q

excess TGFbeta siganlsing causes

A

deleterious effects on vascular smooth muslce integrity

34
Q

marfan - like syndrome

A

not a muation in fibrillin, but a mutation in TGF beta instead

35
Q

Mice and Fibrillin1 mutations

A

mice with muations in fibrillin 1 respond to treatment with anti-TGF beta antibodies, by decreasing the aortic and valve deletrious effects on SM integrity

36
Q

Hypertrophic Cardiomyopathy

A

autosomal dominant - 50% familial - unexplained hypertrophy of left ventrical and interventricualr septum under normal hemodynamic stresses. The hypertrophied septum bulges into the lumen of the left ventricle decreasing left ventricular compliance and increasing left ventricular systolic function.Left atrium is dialated and left cavity is small.

37
Q

Symptoms of hypertrophic cardiomyopathy

A

often asymptomatic at rest, exertional shrotness of breath, risk of sudden death in young athletes –> Herald Sun (hoop star that died)

38
Q

Genetics of hypertrophic cardiomyopathy

A

multiple mutation s in different sarcomeric proteins (70-80%): beta myosin heavy chain and light chain genes, Troponin T and I subunits, Myosin binding protein C, Alpha-Tropomyosin

39
Q

theory of sarcomere and hypertrophic cardiomyopahty

A

incorporation of a mutant polypeptide into the sarcomere alters structure and function – myocytes respond to normal hemodynamic pressures by hypertrophying

40
Q

prognosis of hypertrophic cardiomyopathy

A

differs depending on specific mutation even though clinical manifestations are similar

41
Q

why should you screen for this

A

prevent death

42
Q

what does hypertrophy do for the heart

A

the heart gains strength but loses capacity to dialate and cant inc CO and SV. Bulging out into ventricle with every contraction, this bulging sticks onto the outflow tract able to block it. Also the coronary arteries take off right at the outflow track and so there is a block of the coronary arteries.

43
Q

Polycystic Kidney disease

A

autosomal dominant affecting PKD 1, 2, and 3 , mostly PKD1

44
Q

prevalence of PKD

A

1/(400-1000) live births – fairly common

45
Q

PKD accouns for what percentage of dialysis/transplantation cases

A

10%

46
Q

PKD penetrance

A

high degree of penetrance

47
Q

PKD clinical manifestations

A

clinically silent until the 5th decade or later when renal failure develops. Progressive disorder - not just failure of plumbing to hook up as in retentions cysts

48
Q

PKD1 gene on chromosome

A

16

49
Q

PKD 1 encodes

A

polycystin - a transmembrane protein with a long extracellular domain and a short cytoplasmic domain. Its structure is similar to those proteins known to be involved in extracellular matrix/cel and cell-cell interactions.

50
Q

PKD cysts have

A

increased cell division and secretion suggesting active progression because of inapproprate signals for growth and differentiation.

51
Q

PKD kidney

A

size can be 5 to 6 times larger than a normal kidney

52
Q

PKD is associated with

A

bary anneurysms_..seen in 5th decade of life?

Pathology 2 (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions