Genetics Flashcards
What is personalised medicine?
The idea to use some form of testing to identify a subgroup of patients who respond to treatmet involving genetic testing and understanding molceular pathways
What does personlaised medicine allow you to do?
Separate patients into subgroups of those who will benefit frmo a treatment and exclude those who won’t or will have severe side effects
What clinical signs can be seen in the nails in tuberous sclerosis?
Periungual fibromata
Longitudinal ridging
What is a genodermatoses?
A skin condition caused by a genetic cause
How can tuberous sclerosis present in infants?
Infantile seizures
What is the earlisest cutaenous sign of tuberous sclerosis?
Ash-lead macule
What are all the clinical signs of tuberous sclerosis?
Periungual fibromas Facial angiofibromas Seizures due to tumours in the cortical brain Hamaromas - angiomyolipomas Bone cysts Shagreen patches Enamel pitting
What are angiofibromas often misdiagnosed as?
Acne (erythematous papules) but the defining difference as angiofibromas don’t have comedones
What type of inheritance does tuberous sclerosis show?
Autosomal dominant - denovo mutations are common
What chromosomes are affected in tuberous sclerosis?
Chromosome 9 and 16
TSC1 and TSC2 which code for tuberin and hamartin
What is the chance of passing on a mutation to offspring in classical autosomal dominance?
50-50 chance
What are the different mutation types?
Missence Deletion (in frame) Nonsense (premature stop codon) Deletion (frameshift) Altered splice site
For what conditions is using genetics the most useful in treatment of diseases?
In high penetrance disorders due to the fact that they tend to have one pathway and therefore one drug which can control it
What is genetic heterogeneity?
Mutations at two or more genetic loci that produce the same or similar phenotypes
What is disease expression variability?
Different people are affeced differently - even within the same family
What is epidermolysis bullosa (EB)?
A group of genetic skin fragility conditions that can range for very mild blistering to extensive skin loss with any movement or touching of the skin
What are the three types of EB?
Simplex
Junctional
Dystrophic
What is simplex epipdermolysis bullosa?
Split occurs within the epidermis - mildest form
What is junctional epidermolysis bullosa?
Split occurs within the DEJ
What is dystrophic epidermolysis bullosa?
Split occurs within the dermis of the skin - complicatd by scarring
How many genes are involved in epidermolysis bullosa?
10 genes
How many different types of keratin are there?
2 types - type 1 and type 2
Both are needed for proper structure of the skin
What is haploinsufficiency?
Only one working copy of the gene - therefore there is reduced protein production
What is dominant negative?
Expression of abnormal protein interferes with normal protein function
What is gain of function?
Mutant protein gains a new function, affecting cell processes
What is complete loss of protein?
Autosomal recessive - 2 faulty copies of gene produces no protein at all
What is the risk of passing a mutation to an offspring if the gene is recessive?
1 in 4 risk of an affected child if the parents are both carriers
How many cafe au lait patches are required on the skin to suggest a genetic disease?
More than 5
What are the clinical signs of neurofibromatosis type 1?
Cafe-au lait macules Neurofibromas Plexiform neuroma Axillary or ingunal freckling Optic glioma Lisch nodules Distinctive bony lesion
What is the neurofibromine pathway involved in?
Controls transcription factors for cell growth, specifically Raf, MEK and ERK
What are the genetic factors involved in skin barrier function failure in eczema?
Filaggrin
What are the genetic factors involved in immunology in eczema?
IL-4 and IL-13
What condition will filaggrin mutations cause?
Ichthyosis vulgaris
Histologically what is absent in ichthyosis vulgaris?
Keratihyaline granules containing pro-filaggrin granules
