Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Molecular Foundations of Medicine > Trinucleotide Repeat Disorders > Flashcards

Trinucleotide Repeat Disorders Flashcards

1
Q

examples of trinucleotide repeat disorders

A
  • fragile x
  • friedreich’s ataxia
  • huntington’s disease
  • mytonic dystrophy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

mechanism of trinucleotide repeat disorder

A
  • expansion of number of repeats

* likely due to slipped DNA mispairing

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

unstable repeat expansions

A
  • number of repeats may increase in offspring

* key: genetic abnormality changes over time

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

anticipation

A
  • phenomenon where disease severity worse in subsequent generations with earlier onset
  • due to more repeats accumulating in abnormal gene
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

fragile x inheritance

A

x linked dominant

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

gene involved in fragile x

A
  • FMR1 gene = fragile x mental retardation 1

* q arm of x chromosome

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

increase in CGG repeats in fragile x leads to

A

DNA methylation of FMR1 gene -> silencing

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

2nd most common cause of intellectual disability

A

fragile x (down syndrome 1st)

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

common features in fragile x

A
  • long narrow face
  • large ears
  • large jaw
  • macroorchidism (after puberty)
  • CT findings (joint laxity)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

associated mental problems with fragile x

A
  • anxiety
  • ADHD
  • often features of autism
  • OCD
  • aggression
  • depression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

friedreich’s ataxia inheritance

A

autosomal recessive

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

friedreich’s ataxia gene

A
  • frataxin (FXN) gene on chromosome 9

* needed for mitochondrial function

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

increased GAA repeats in freidreich’s ataxia causes

A

decreased frataxin levels -> mitochondrial dystunction

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

frataxin protein

A
  • mitochondrial protein
  • high levels in brain, heart, pancreas
  • abnormal -> mitochondrial dysfunction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

presentation of friedreich’s ataxia

A
  • typical onset 5-15 yo

* cerebellar and spinal cord degeneration -> loss of balance and weakness

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

physical deformities that commonly develop in friedreich’s ataxia

A
  • kyphoscoliosis

* foot abnormalities (pes cavus)

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

common problem associated with friedreich’s ataxia

A
  • hypertrophic cardiomyopathy
  • a-fib -> tachycardia
  • diabetes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

huntington’s disease inheritance

A

autosomal dominant

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

gene and location in huntington’s disease

A
  • HTT gene located at 4P16.3

* codes for protein huntington

20
Q

what does CAG expansion cause in huntington disease

A
  • CAG codes for glutamine

* polyglutamine disorder

21
Q

cause of symptoms in huntingtons disease

A
  • degeneration in basal ganglia (striatum)
  • leads to dementia, chorea, ataxia, dysarthria (difficulty with formation of speech)
  • death usually 10-20 years after diagnosis
22
Q

myotonic dystrophy inheritance

A

autosomal dominant

23
Q

type 1 myotonic dystrophy gene

A
  • DMPK gene on chromosome 19
  • codes for myotonic dystrophy protein kinase
  • abnormal gene transcribed to mRNA but not translated
24
Q

presentation of myotonic dystrophy

A
  • most commonly begins in adulthood (20-30yo)
  • progressive muscle wasting/weakness
  • myotonia (prolonged muscle contractions)
    • unable to relax muscle after use
    • cannot release grip
    • locking of jaw
25
facial characteristics in myotonic dystrophy
* facial muscles often affected -> weakness/wasting-> | * long narrow face and hollowed cheeks
26
other problems found in myotonic dystrophy
* multisystem disorder: * hypogonadism * cataracts * cardiac arrhythmia * frontal balding * insulin resistance * arrhythmias (atrial flutter and fibrillation) * 1st degree AV vlock * bundle branch block * respiratory complications * intellectual disability (worse with earlier onset)
27
where can trinucleotide repeat expansions occur
•coding or non-coding regions of gene (anywhere in gene)
28
causes of trinucleotide repeat expansions
•gene conversion (unequal crossing over) during meiosis OR mistakes in: •DNA replication •double-stranded DNA break repair •base excision repair of oxidative damage •single-stranded DNA gap repair
29
where would you find high expression of huntington protein
testes and brain
30
function of huntington protein
* found in nucleus and cytoplasm * regulates intracellular transport of many proteins * shuttles transcription factors in and out of nucleus * may sequester TFs * required for normal embryonic devand neurogenesis
31
Expansion of CAG region in huntington disease results in
aggregation of the mutant protein into inclusion bodies
32
where does the CAG repeat expansion occur in huntingtons disease
exon I
33
hypothesis of expansion mechanism in huntington disease
meiotic instability in sperm -> unequal crossing over
34
common differential diagnosis in patient with suspicion for fragile x
* down syndrome * williams syndrome * angelman * autism spectrum disorer
35
location of trinucleotide repeat expansion in fragile x
* near the promoter in 5' UTR of FMR-1 gene, which encodes FMRP * silences the promoter
36
FMRP implicated in
* dendritic spine maturation * synapse formation * synaptic plasticity
37
associated problems with fragile x
* mitral valve prolapse * HTN * sz activity * possible strabismus * hypotonia * pes planus
38
common symptoms of freidreich ataxia
* muscle weakness in arms/legs * loss of coordination * vision/hearing impairment * slurred speech * scoliosis * pes cavus
39
spinal cord change in friedreich ataxia
* spinal cord becomes thinner | * nerves lose part of myelin sheath
40
what does frataxin protein do
•removes iron in the cytoplasm and around mitochondria
41
iron buildup in mutant frataxin protein
* causes free radical damage to mitochondrial membrane * oxidative stress * esp affects nerves and muscle cells
42
location of trinucleotide expansion in friedreichs ataxia
first intron on FXN gene -> transcriptional repression
43
compound heterozygotes in friedreichs ataxia
* 4% of patients | * have expansion in 1 allele and some other mutation of FXN in other allele
44
treatment of friedreichs ataxia
* supportive: scoliosis surgery if indicated, cardia meds, DM meds, PT * genetic counseling: * 25% recurrence risk (AR) * carrier frequency is 1/110, affects 1/50,000 in US
45
location of trinucleotide repeat expansion in myotonic dystrophy
3' intron
46
location of trinucleotide repeat expansion in huntington disease
exon 1

Molecular Foundations of Medicine (21 decks)

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