Genetics - Cases and Mechanisms

Question 1

what is precision medicine?

Answer 1

using some form of testing to identify a subgroup of patients who respond to a treatment
can involve genetic testing

Question 2

what is precision medicine used in right now?

Answer 2

cancer

some diseases

Question 3

what is the benefit of precision medicine?

Answer 3

can test whether treatment will be effective in people so people will get effective treatment instead of giving everyone the same and it not working for some

Question 4

what are periungual fibromata? are they always pathological?

Answer 4

fibrous, bulbous overgrowths at cuticle of nail

one can be normal but many is pathological

Question 5

what is periungual fibromata diagnostic of?

Answer 5

tuberous sclerosis

Question 6

what is tuberous sclerosis?

Answer 6

autosomal dominant genodermatoses

causes infantile seizures and can produce ash leaf macules in skin (depigmented)

Question 7

how can ash leaf macules be seen on pale skin?

Answer 7

woods lamp

Question 8

what are the signs of tuberous sclerosis?

Answer 8

periungual fibromas
facial angiofibromas
cortical tumours - epilepsy
hamartomas - angiomyolipomas
bone cysts
shagreen patches
enamel pitting

Question 9

what are angiofibromas?

Answer 9

erythematous papules
can be misdiagnosed as acne, but doesn’t form comodones
begin in first year of life and progress through life

Question 10

what causes tuberous sclerosis?

Answer 10

autosomal dominant mutation in either 9q34 or 16p13.3 AFFECTING TSC1 and TSC2 genes (codes for tuberin and hamartin - tumour regulating genes)

Question 11

is tuberous sclerosis always inherited?

Answer 11

not always

can be a spontaneous mutation

Question 12

are new mutations common?

Answer 12

yes
can have around 120 new mutations that aren’t present in parents
depends on how old father is (older = more mutations)

Question 13

% chance of being affected by autosomal dominant mutation if parent is affected?

Answer 13

50%

but disease not always shown

Question 14

how does a mutation cause a problem?

Answer 14

affects central dogma

i.e can effect protein synthesis

Question 15

what are the types of mutation?

Answer 15

missence - single nucleotide mutation
deletion (in frame) - deletion of a codon
Premature stop - premature stop codon
deletion (frameshift) - deletion of a number of nucleotides not divisible by 3

Question 16

give an example of a treatment created through precision medicine?

Answer 16

rapamycin

Question 17

what type of mutation does precision medicine work best for?

Answer 17

high penetrance disorders

Question 18

how does precision medicine work?

Answer 18

identify genes for a disease which tells you the pathway

pathways can then be targeted for treatments

Question 19

what is genetic heterogeneity?

Answer 19

the causative mutation in a genetic disease can be in one of two genes

Question 20

skin of baby blistered at birth which then progresses to extensive skin loss occurring with any movement/handling of baby?

Answer 20

EB - Epidermolysis Bullosa

Question 21

what is EB?

Answer 21

group of genetic fragility conditions

variable severity of blistering and skin loss

Question 22

what is EB?

Answer 22

group of genetic skin fragility conditions

variable severity of blistering and skin loss

Question 23

simplex type?

Answer 23

split in epidermis, surface of blister is upper epidermis

almost normal life, just blister very easily

Question 24

simplex type EB?

Answer 24

split in epidermis, surface of blister is upper epidermis

almost normal life, just blister very easily

Question 25

junctional type EB?

Answer 25

split is at dermo-epidermal junction | heals with scarring

Question 26

dystrophic type EB?

Answer 26

split is in the dermis | cant heal, causes extensive scarring (mitten deformity)

Question 27

types of keratin?

Answer 27

type 1 and type 2 which bind to form a dimer > tetramer giving structural integrity

Question 28

what are the types of keratin and what do they do?

Answer 28

type 1 and type 2 which bind to form a dimer > 2 dimers form a tetramer giving structural integrity

Question 29

through what 4 mechanisms can a mutation cause a disease?

Answer 29

good gene not producing enough (e.g protein) so deficiency causes disease = haploinsufficiency OR mutation makes abnormal protein which stops the normal protein working = dominant negative (more severe effect) mutant protein gains new function affecting cell process = gain of function 2 faulty copies of gene produce no protein = complete loss of protein (autosomal recessive)

Question 30

how can mutations arise in offspring when the parents don't have the mutation?

Answer 30

new mutation occurs in one parents gametes | one parent is mosaic so has some copies of mutation but not all

Question 31

asymptomatic coffee coloured flat marks?

Answer 31

café au lait macules | >5 indicates neurofibromatosis type 1

Question 32

clinical signs of neurofibromatosis?

Answer 32

``` café au lait macules neurofibromas (soft and squishy tumours) axillary/inguinal freckles plexiform neuroma optic gliomas (eye tumours) Lisch nodules Bony lesions ```

Question 33

is neurofibromatosis autosomal dominant?

Answer 33

``` quite often (50-60%) or can be a new mutation ```

Question 34

what does neurofibromine do?

Answer 34

involved in cell growth

Question 35

red, rough patches of skin at 2 weeks old which becomes more itchy and broken?

Answer 35

atopic eczema

Question 36

which components of atopic eczema do genetic factors effect?

Answer 36

skin barrier effect (filaggrin) and immunology (interleukin 4 and 13)

Question 37

what does a filaggrin mutation cause?

Answer 37

hyperlinear palms (wrinkly) dry skin more severe ichthygosis vulgaris effects if both copied affected has a role in atopic diseases

Question 38

what does a filaggrin mutation cause?

Answer 38

hyperlinear palms (wrinkly) dry skin more severe ichthygosis vulgaris effects if both copied affected has a role in atopic diseases

Question 39

what can a filaggrin mutation predispose to?

Answer 39

``` atopy hayfever asthma eczema food allergy (esp. peanuts) due to leakiness caused ```

Question 40

are most human diseases monomeric?

Answer 40

no | most are comlex - many genes interacting with many environments