Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

KCSU17 Genetics > Autosomal Dominant Disorders > Flashcards

Autosomal Dominant Disorders Flashcards

(66 cards)

Start Studying
1
Q

pleiotropy

A

when one gene effects multiple phenotypic traits and symptoms

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

age of onset of HD

A

typically 30-50 years old

progresses over 15 years and culminates in death

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

genetic abnormality of huntington’s disease (HD)

A

short arm of chromosome 4

mutation is a CAG expanded reapeat in the coding portion of hte gene

autosomal dominant

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

number of CAG repeats and Huntington’s Disease

A

Normal= 1-26

27-35 = unaffected

36+ = disease present, incomplete penetrance with 36-41

*** the larger number of repeats = earlier age of onset

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

protein affected in HD

A

huntingtin

involved in transport of vesicles in cellular secretory pathways

req. for normal produciton of BDNF

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

HD causes neuro degeneration of which areas in brain?

A

Basal ganglia (movement)

cortex (thoughts, memory)

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

Basal Ganglia

A

located on inner brain

control and coordination, muscle movement

HD specifically targets neurons of striatum (caudate nuclei and pallidum)

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

Cortex

A

outer surface of the brain

involved in perception, memory, and thought

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

Huntington’s disease pathophysiology

A

mutution in chromosome 4 causes increas in CAG repeats near huntingtin’s AA terminal

build up of CAG repeats causes production of abnormal huntingtin protein –> causes cell death

gain of function disease – over expression of abnormal huntingtin protein

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

HD imaging

A

loss of neurons on MRI

PET scan shows decreased glucose uptake in brain

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

clincial manifestations of HD

A

disease leads to brain weight loss (25% +)

  • a progressive loss of motor control
    • non-repetitive jerks; abnormal body movements that worsen over time
  • psychiatric problems
    • psychosis and schizophrenia
    • cognitive abnormalities dementia
  • behavioral disturbances
    • aggression, outbursts

HD patients eventually won’t be able to walk. Aspiration pneumonia (difficulty swallowing) is what causes death most often. The clinical course of HD is protracted (drawn out: 15-18 years before death)

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

HD:

Loss of motor control results in excessive uncontrollable movements of the head, face, trunk and limbs, controlled by?

A

basal ganglia

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

HD

Alterations in thought, perception, and memory are controlled by?

A

Cortex

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

HD expression

A

95% of cases are inherited (5% spontaneous)

affected homozygots display same course as heterozygotes

larger number of CAG repeats = earlier onset of disease

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

Juvenile Huntington Disease

A

HD onset before 20 years of age

paternally transmitted

esp. large number of repeats (>60 CAG repeats)

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

maternal v. paternal expression of HD

A

when the father transmits the disease there is a tendency for greater CAG repeat expansion

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

HD penetrance

A

incomplete pentrance occurs between 36-41 repeats

full penetrance occurs at >41

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

HD treatment

A

no curative treatment

drugs are available to treat symptoms

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

most common form of muscular dystrophy in adults

A

Myotonic Dystrophy

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

Genetic abnormality in Myotonic Dystrophy

A

autosomal dominant

nucleotide repeat expansion of CTG in DMPK on chromosome 19

number of repeats determins the degree of severity

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

CTG repeats in MD

A
  • 5 to 30 CTG repeats = unaffected individuals
  • 50 to 100 CTG repeats = mildly affected
  • 100 to 2000 CTG repeats = severely affected
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

myotonic dystrophy (summary)

A
  • most common form of muscular dystrophy seen in adults
  • characterized by progressive muscle deterioration.
  • Caused by an abnormal nucleotide repeat expansion (CTG) in a non-coding region of DMPK gene on chromosome 19
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

protein affected in MD

A

DMPK

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

pathophys of MD

A

The mutation is an expanded CTG trinucleotide repeat

The number of these repeats is strongly correlated with severity of the disease (like HD with CAG).

affect multiple systems: skeletal m, cardiac arrhythmias, and cataracts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
clincial manifestation of MD
Onset is usually prominent in the **2nd or 3rd generation**; lifespan is typically six decades **Muscle weakness** and **wasting** in the arms and legs and **myotonia** (muscle spasms/stiffening) tends to be the 1st symptoms noticed.
26
expression of MD
number of repeates increases with suceeding generations (anticipation) number of repeats correlated with severtiy of disease can be seen in infancy
27
congential MD
inherited from the mother presents in infancy characterized by an _inverted “V” shaped upper lip_ and c_ompromised respiratory function_ (what generally kills them)
28
MD penetrance
incomplete penetrance at 50-100 CTG repeats full penetrance at 100-2000 CTG repeats
29
MD treatment
anti-seizure medicin to treat myotonia requires lots of PT/OT to treat muscle weakness and wasting
30
HD general
* autosomal dominant * a neurodegenerative disease that affects certain areas of the brain * Onset is dependent on age * typically 30-50 years old * progresses over 15 years * very rapidly, and culminates in death * Specifically affects cells of the basal ganglia * polyglutamine disease * involves expanded CAG repeats in gene product * affecting huntingtin protein * chromosome 4.
31
Marfan Syndrome (general)
heritable disorder of connective tissue that affects fibrillin protein; it results in excessively “stretchy” connective tissue that allows for bone overgrowth to occur
32
genetic abnormality in Marfan syndrome
**autosomal dominant** mutation located on **chromosome 15 gene** that encodes fibrillin
33
protein affected in Marfan Syndrome
**fibrillin** connective tissue protien, major cmoponent of microfibrils (suspensory ligaments of lens, aorta, and periosteum)
34
pathophys of marfan syndrome
mutated fibrillin gene = **excessively stretchy connective tissue** body systems affected: skeleton, heart and vessels, eyes, nervous system, skin, lungs
35
skeletal clinical manifestations of Marfan
taller than average chest wall deformiteis **steinberg thumb sign**
36
clinical manifestations of marfans cardiovascular
widening of ascending aorta can lead to CHF (must montitor)
37
clinical manifestations of marfans nervous
out poaching of dura in spinal cord = **dura ectasia**
38
clincial manifestations of marfan's eyes
dislocation of one or both lenses of the eye
39
clincial manifestations of marfan's skin
stretch marks
40
clincial manifestations of marfan's lungs
connective tissue abnormalities makes lungs less elastic --\> causes lung collapse
41
expression and penetrance pattern of marfan's
40% of cases are spontaneous (60% inherited) if parent has marfan, 50% risk they will pass gene to off spring **variable expression** -- same genotype can have large variety of phenotypes
42
Marfan's treatment interventions
require annual evaluations to detect changes in spine/sternum must monitor for changes in defects, adverse effects reg. eye exam, no smoking, avoid exercise, pregnancy risk
43
Neurofibromitosis Type I general
most common autosomal dominant disturbs cell growth in nervous system causes tumors to form on nervous tissue Type 1 is 90% of cases, 50% of cases result from new mutation
44
Neurofibromitosis Type I genetic abnormality
type I is mapped to a gene on chromosome 17q lg. gene = mutation target (accoutns for high mutation rate) type 2 is chromosome 22
45
Neurofibromitosis Type I protein affected
encodes mRNA transcript and gene product: **neurofromin** protein that acts as a tumor suppressor
46
pathophysiology Neurofibromitosis Type I
affected individuals develop tumors **cutantous neurofibromas** are classic symptom
47
Neurofibromitosis Type I clincical manifestaitons
cutaneous neurofibromas (nodules/tumors on skin) learning disabilities lisch nodules (tumors on iris) *Cafe-au-lait* (hyper pigmented skin) NF1 is suspected if only 2+ present *tinnitus is present instead of iris nodules in NF2*
48
Neurofibromitosis Type I expression and penetrance pattern
highly variable expression
49
retinoblastoma (general)
most common childhood eye tumor occurs during embryonic development when retinal cells are actively dividing/proliferating Almost always presents by 5 years of age (40% familial/60% spontaneous mutations).
50
genetic abnormality Retinoblastoma
chromosome 13 autosomal dominant, sporadic and non hereitary
51
retinoblastoma protein affected
RB1 gene
52
Retinoblastoma types and expression
Non-hereditary (60% are spontaneous) and sporadic (not transmitted) affected individuals will transmit gene to half of offspring (familiar ones are multi focal and bilateral)
53
retinoblastoma penetrance
**reduced penetrance** not everyone with genotype gets phenotype because *it requires a second hit* in the same region of the DNA
54
retinoblastoma treatment interventions
treated with radiation, cryotherapy or laster photocoagulation detected with the white light shown on the eye
55
Retinoblastoma reading assignment
**There is reduced penetrance in inherited retinoblastoma because the normal RB1 allele requires a second hit in order for the tumor to develop.** The second hit has a low probability of occurring in any given cell. Because the second hits are random events, a small fraction of persons who inherit the disease allele never experiences a second hit in any retinal cell and thus do not develop retinoblastoma. **The requirement for the second hit thus explains the reduced penetrance seen in the disorder.**
56
Factor V Leiden
autosomal dominant condition that results in factor V protein variant that can not be degrated by aPC **blood clotting factor** can easily lead to thromboembolism
57
aPC
protein responsible for breaking down blood clot formed by factor V
58
Achondroplasia
aka dwarfism disorder of bone growth most common type of short-limbed dwarfism **unable to convert cartilage to bone**, particularly in the long bones of the arms and legs
59
Achondroplasia Genetic abnormality
mutation on the **FGFR3 gene**
60
Achondroplasia protein affeted
protein made by FBFR3 receptor that regulates bone growth by limiting formation of bone from cartilage (**ossification**)
61
Achondroplasia pathophys
FGFR 3 gene mutated becomes overly active, interfearing with ossification and leads to disturbances with bone growth= **short stature** bc this disease is in the long bones, it results in **average size trunk** **normal intelligence is seen with this disease**
62
Achondroplasia clinical manifestations
short arms and legs byt average size trunk breathing disorder (apnea) normal intelligence
63
Achondroplasia expression and penetrance
trait appear in every generation transmitted from either parent
64
similaries between HD and MD
**autosomal dominant** with anticipation and early onset form longer the repeat, earlier the disease occurs
65
differences bt MD and HD
MD early form is from the mother, presents at birth HD early form is paternal, presents in teens HD mutation is on chromosome 4 with CAG repeats,MD mutation is chromosome 19 with CTG HD fully penetrant at \>41 repeats and affects huntingtin. MD is fully mutant 50-2000 repeats and affects and DMPK
66

KCSU17 Genetics (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions