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Flashcards in Genetics Deck (35):
1

What is an example of an X-linked recessive neuro disease?

Duchenne muscular dystrophy

2

What is an example of an AD neuro disease?

Huntington's

3

What are some examples of neuro diseases displaying heterogeneity/are multifactorial?

Alzheimer's
MS

4

What does DMD cause?

Delay in motor development
Wheelchair bound by 10-12y
Death from involvement of respiratory and cardiac muscle in 20s
Male incidence 1:3000

5

When and where does the onset of DMD occur?

~3-4 years in the pelvic and shoulder girdles

6

What feature occurs in DMD and Becker muscular dystrophy?

Calf hypertrophy

7

Why does DMD occur?

Deletion of dystrophin gene in 70% DMD boys
Point mutations, small insertions and deletion in remaining 30%

8

How is DMD diagnosed?

Developmental delay in boys
Muscle weakness- Gower's, toe walking
Raised CK
EMG
Muscle Biopsy
Molecular genetic testing

9

What may be included in a DDx of DMD?

Autosomal recessive limb girdle muscular dystrophies-some caused by sarcoglycan deficiencies

10

What carrier testing occurs in DMD?

Identify mutation in affected boy
Test for mutation in female relatives wishing to know status
Female carriers of dystrophin mutations can be offered prenatal/pre-gestational testing

11

What histological findings are seen in DMD?

No spinal cord or nerve abnormality
Muscle tissue has extensive granulation and the sarcolemma is broken down and destroyed

12

What is Huntington's disease?

AD progressive neurodegenerative disorder
Incidence 1:20000

13

What happens in Huntington's disease?

Onset between 30-50
Involuntary movements
Dementia
Progression to severe dependency and death over 15-20 years

14

What is the penetrance of Huntington's?

Age dependant (variable)

15

What are some early clinical signs of Huntington's?

Clumsiness
Agitation
Irritability
Apathy
Anxiety
Disinhibition
Delusions/Hallucinations
Abnormal eye movements
Depression

16

What are the later clinical signs of Huntington's?

Dystonia
Involuntary movements
Trouble with balance and walking
Trouble with activities that require manual dexterity
Slow voluntary movements
Difficulty initiating movement
Inability to control speed and force of movement
Weight loss
Speech difficulties
Stubbornness

17

What are the late clinical signs of Huntington's?

Rigidity
Bradykinesa
Severe chorea
Serious wt loss
Inability to walk
Inability to speak
Swallowing problems
Inability to care for oneself

18

What atrophies in Huntington's?

Caudate nucleus

19

Where is the genetic defect in HD?

CAG gene- codes for glutamine

20

What genetic principle does Alzheimer's display?

Heterogeneity

21

What pathology occurs in Alzheimer's?

Loss of cortical neurones
Neurofibrillary tangles (intracellular)
Senile plaques (extracellular)

22

What do the senile plaques in Alzheimer's contain?

Amyloid Beta protein- a fragment of the product of the amyloid precursor protein (APP) gene

23

Where is the APP gene found?

Ch 21

24

What inheritance can early onset Alzheimer's display?

AD in 5-10% cases

25

What condition can be considered a genetic cause for Alzheimer's?

Down syndrome (onset in 3rd to 4th decade)

26

Where are the mutations present in AD Alzheimer's?

APP (Ch 21)
Presenilin 1 (Ch 14)
Presenilin 2 (Ch 1)
Others

27

Presenilins are a component of what secretase?

Gamma-secretase

28

What polymorphism has been shown to cause Alzheimer's?

Apolipoprotein E (ApoE)

29

What ApoE alleles cause Alzheimer's and in how many of the population are they present ?

e4 17%
e3 72%
e2 11%

30

How many people will be affected by Alzheimer's with an e4/e4 genotype?

55% by 80yo

31

How many people will be affected by Alzheimer's with an e3/e4 genotype?

27% by 85yo

32

How many people will be affected by Alzheimer's with a no e4 genotype?

9% by 85yo

33

What does the e4 allele predispose to?

Alzheimer's with some clustering in families

34

What is the e2 allele associated with?

Longetivity

35

What genetic pattern does MS display?

Multifactorial- clustering in families.
First degree relative 3% risk, second degree 1%