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Flashcards in Neurogenetics Deck (40):
1

what type of inheritance is duchenne MD

x linked recessive

2

what is the onset and progression of duchennes

delay in motor development
onset of weakness 3-4 years (pelvic and shoulder girdle)
wheelchair bound by 10-12 years
death from involvement of respiratory and cardiac muscles

3

what is the characteristic posture of duchennes

accentuated lumbar lordosis

4

what hypertrophies in duchennes

calf muscles

5

what causes duchenes

mutation in dystrophin gene in X chromosome that causes a dystrophin deficiency (dystrophin connects the contractile elements of the cell- muscle cells unable to renew and so degenerate with age)

6

what are the majority of mutations in duchennes

large scale mutations (70%)

7

how is duchennes diagnosed

gowers sign, toe walking
raised serum CK
electromyography (EMG)
muscle biopsy (not done as painful)
molecular genetic testing

8

what is autosomal recessive limb girdle muscular dystrophies

dystrophy similar to duchennes
mutation not in X chromosome so affects boys and girls equally in a recessive pattern

9

why are females protected from x linked conditions

as have other working x chromosome

10

if a mother is carrier of duchennes what is the chance of a son getting it

1 in 2

11

how many cases of duchennes are not inherited but caused by a new mutation

1/3rd

12

how prevelant is duchennes

1 in 3000

13

what mutation testing can be done in duchennes

can identify in affects or in female carriers
pre natal testing in female carriers

14

what is the screening test for duchennes

serum CPK

15

how prevelant is huntingtons disease

1 in 20,000

16

what is huntingtons disese and its symptoms

progressive neurodegenerative disorder
-onset between 30-50
-involuntary movements
-dementia
-progresses to severe dependency and death

17

what is the inheritance of huntingtons

autosomal dominant
age dependant penetrance

18

what are the early clinical signs of huntingtons

clumsiness
agitation
irritability
apathy
anxiety
disinhibition
delusions, hallucinations
abnormal eye movements
depression

19

what are the intermediate clinical signs of huntingtons

dystonia
involuntary movements
balance and gait problems
reduced manual dexterity
slow voluntary movements
difficulty initiating movements
inability to control speed and force of movement
weight loss (swallowing difficulties)
speech difficulties (dysarthric speech)
stubborness

20

what is dystonia

sustained or repetitive muscle contractions result in twisting and repetitive movements or abnormal fixed postures

21

what are the late clinical signs of huntingtons

rigidity
bradykinesia (difficulty initiating and continuing movements)
severe chorea
serious weight loss
inability to walk
inability to speak
swallowing problems, danger of choking
dependence

22

what is caudate atrophy

loss of cortical tissue (caudate nuclei- usually project into the lateral ventricles)
get it in huntingtons

23

what causes huntingtons

mutations in the huntingtons gene
CAG (Codes for glutamine- in huntingtons this gene is expanded causing an accumulation of glutamine which has a neurotoxic effect)

24

why does huntingtons have earlier onset in each generation

as more repeats of the CAG gene get added each generation- neurogenerative condition

25

what does age dependent penetrance in huntingtons mean

the older you get the lower your risk of getting the condition

26

what genetic testing is done for huntingtons

pre natal and pre gestational
no known treatment to stop progession so essential to have informed consent

27

what is spinal muscular atrophy

a neurodegenerative disorder that causes progressive loss of anterior horn cells in spinal cord and brain stem nuclei

28

what is the inheritance of spinal muscular atrophy

autosomal recessive
variable age of onset and rate of progression (types 0-4 depending on age of onset)

29

what are the features of spinal muscular atrophy

proximal muscles weakness
tongue fasciculation

30

what causes spinal muscular atrophy

SMN1 deficiency (essential for survival of LMNs) due to mutation making gene unable to make mRNA

31

if both parents are carriers for spinal muscular atrophy what is the chance of the child being affected

1 in 4

32

how do drugs work against spinal muscular atrophy

mRNA which alters the pattern of slicing and allows it to retain the exon (exon 7) that would be missing in the disease- retains the proteins that would be deficient
Drug needs to be intra-thecal injected = lumbar puncture

33

what condition does alzheimer disease cause

dementia

34

who gets alzheimers

usually occurs in old age
can cause pre senile dementia
some clustering in families

35

what causes alzheimers

loss of cortical neurones
neurofibrillary tangles (intracellular proteins)
senile plaques (extracellular protein deposits)

36

what are senile plaques

extracellular protein deposits containing amyloid beta protein

37

what is the inheritance of alzheimers

autosomal dominant in 5-10% of cases (usually early onset)
common multifactoral forms

get it in down syndrome (onset in 3rd or 4th decade)

is genetically heterogenious (same phenotype produced)

38

what mutations cause autosomal dominant alzheimers

APP (amyloid precursor gene- senile plaques)
presenilin 1 and 2 (more common than APP)
ApoE (associated with familial clusters)

(APP gene involves in splicing secretase)

39

what are the types of ApoE genotypes associated with in alzheimers

E4 prediposes to the disease with clustering in families
E2 associated with longevity and old age without the disease

40

what is the inheritance of multiple sclerosis

multifactoral - polygenic
some clustering in families