Genetics Flashcards
What is the function of precision medicine?
To identify multiple small subgroups who will respond to their own specific treatments
What condition can present as Periungual fibromatas and longitudinal ridging of the nails?
Tuberous sclerosis
What other clinical features point towards a diagnosis of Tuberous sclerosis
infantile seizures
cutaneous sign = ash-leaf macule
Shagreen patches
Enamel pitting in teeth
What tumours can Tuberous sclerosis cause?
Facial angiofibromas
Cortical tubers (causes the seizures)
Hamartomas
Bone cysts
Is Tuberous Sclerosis an autosomal dominant or recessive disorder?
autosomal dominant
Lots occur as de Novo mutations - aka first person in the family to have it
What do the TSC1 and TSC2 genes encode for?
tuberin (chromosome 9) and hamartin (chromosome 16)
Tumour regulating genes – in the same pathway
Why is it always important to check family history in conditions such as Tuberous Sclerosis?
Sometimes family members are unaware they have the condition as they do not display all symptoms
How many new mutations does the average child have, that their parents don’t?
around 120
What can affect the number of new mutations a child has?
The age of the father
Due to spermatozoa going through more cell division, => more opportunities for mutations to occur at meiosis
What specific treatment is used in Tuberous sclerosis?
mTOR inhibitors
What genetic disorder presents with blistering and ulceration of the newborn? (not due to delivery trauma)
Epidermolysis Bullosa (EB)
In Epidermolysis Bullosa, does blistering at birth determine prognosis?
No, the disease can vary in severity
What are the three main types of Epidermolysis Bullosa?
EB Simplex
Junctional
Dystrophic
Is Epidermolysis Bullosa autosomal dominant or recessive?
Can be dominant, recessive, a new mutation or acquired in the environment
What layer of the skin is affected in EB Simplex?
The epidermis is split and keratinocytes fall apart
=> leads to blistering at surface of dermis
What layer of the skin is affected in Junctional EB?
The dermo-epidermal junction
What layer of the skin is affected in Dystrophic EB?
The dermis
this is then complicated by scarring
Describe the difference in scarring between the epidermis and dermis
If the EPIDERMIS ONLY is traumatised, there will be no scarring when it heals
If the dermis (or anything from the dermo-epidermal junction downwards) is damaged, this will SCAR on healing.
Describe the normal pathway of keratin filament assembly
Type 1 and 2 Keratin form a dimer -> Tetramer -> filament
Describe the term HAPLOINSUFFICIENCY
During autosomal dominant disorders, the correct protein can still be produced, just not ENOUGH
What genetic term is used to describe the situation where an autosomal dominant disorder produces the wrong shape of protein, causing the normal protein to stop working?
Dominant Negative
What genetic term describes a patient who has two faulty copies of a gene, causing a complete loss of the desired protein?
Autosomal Recessive
Describe the appearance of Café-au-lait macules
asymptomatic coffee coloured flat marks
How many café-au-lait macules indicate genetic disease?
> 5 macules
What genetic disease is characterised by café-au-lait macules
Neurofibromatosis (Type 1)
Apart from café-au-lait macules, what other clinical feature can distinguish neurofibromatosis?
Neurofibromas (soft neural tumours) Axillary or inguinal freckling Optic glioma 2 or more Lisch nodules (brown marks on iris) A distinctive bony lesion
What targeted treatment is offerered to those suffering from Neurofibromatosis type 1?
MEK inhibitors
What genetic factors influence atopic eczema?
Filaggrin function mutation (1 in 10)
=> resulting in ichthyosis vulgaris
What is the function of filaggrin in atopic disease?
Acts as a skin barrier
By how much does a filaggrin mutation increase the risk of atopic disease?
Increases risk of eczema 4X
Increases risk of asthma and hay fever ≈3X
Increases risk of peanut allergy 5X
