8: Genetics - tuberous sclerosis, epidermolysis bullosa, NF type 1

Question 1

What is the biggest factor contributing towards your chance of having a mutation?

Answer 1

Age of the father

Question 2

A patient presents with periungual fibromata and longitudinal ridging in their toenails.

What is a periungual fibroma?

What genetic condition do they have?

Answer 2

Small lesions found at the nail folds

Tuberous sclerosis

Question 3

What is an early neuro sign that a person may have tuberous sclerosis?

Answer 3

Infantile seizures

Question 4

What is the mode of inheritance for tuberous sclerosis?

Answer 4

Autosomal dominant

Question 5

Can tuberous sclerosis develop spontaneously in an adult? If so, why?

Answer 5

Yes

Spontaneous mutation

Question 6

Mutations in which genes are responsible for tuberous sclerosis?

Answer 6

TSC1

TSC2

Question 7

What type of genes are TSC1 and TSC2?

Answer 7

Tumour suppressor genes

Question 8

Which specific proteins do TSC1 and TSC2 code for?

Answer 8

TSC1 - hamartin

TSC2 - tuberin

Question 9

What is the earliest cutaneous sign of tuberous sclerosis?

Answer 9

Ash-leaf macules

Question 10

Which piece of equipment can be used to better visualise ash-leaf macules?

Answer 10

Wood’s lamp

Question 11

What are ash-leaf macules?

Answer 11

Depigmented macules which look like trees

Question 12

What are facial angiofibromas?

Answer 12

Brown lesions on the face

Question 13

Cortical tubers are another sign of tuberous sclerosis. What can they cause?

Answer 13

Seizures

Question 14

What are hamartomas?

Where can they be found in tuberous sclerosis?

Answer 14

Benign growth malformations which resemble neoplasms

Heart, lungs, kidneys

Question 15

What happens to the tooth enamel in tuberous sclerosis?

Answer 15

Pitting

Question 16

What are Shagreen patches?

Where are they found?

Answer 16

Connective tissue lesions which look like orange peels

Lower back

Question 17

Name five signs of tuberous sclerosis.

Answer 17

Seizures

Ash-leaf macules

Periungual fibromas

Facial angiofibromas

Cortical tubers

Hamartomas

Shagreen’s patches

Pitting of tooth enamel

Bone cysts

Question 18

Autosomal dominant conditions are seen in (all / some) generations.

Answer 18

all generations

Question 19

If a parent is affected by an autosomal dominant condition, what are the chances of their child inheriting it?

Answer 19

50%

Question 20

What two characteristics of autosomal dominant conditions are variable?

Answer 20

Expressivity (whether it is severe or not)

Penetrance (whether it presents or not)

Question 21

Are males and females equally likely to inherit an autosomal dominant condition?

Answer 21

Yes

Question 22

During transcription, (introns / exons) are removed from DNA.

Answer 22

introns

Question 23

(Introns / exons) are vital for RNA and protein expression.

Answer 23

Exons

Question 24

Which experimental drugs may be used to treat tuberous sclerosis?

Answer 24

mTOR inhibitors

Question 25

Tuberous sclerosis shows **genetic heterogeneity**. What does that mean?

Answer 25

The mutation can be in either **TSC1** or **TSC2** and the disease will still present itself

Question 26

Some people have the mutation but don't show features of the disease at all - its ___ is variable. Tuberous sclerosis has varying severity in different people - its ___ is variable.

Answer 26

**penetrance** **expressivity**

Question 27

Is **tuberous sclerosis** a: **Mendelian disorder** (with high penetrance but low frequency) or a **Multifactorial disorder** (with low penetrance but high frequency)?

Answer 27

**Mendelian disorder**

Question 28

What is epidermolysis bullosa?

Answer 28

**A group of genetic skin fragility conditions** Causes skin loss and blistering on gentle handling of patient

Question 29

Is epidermolysis bullosa **autosomal dominant** or **recessive**?

Answer 29

**All of the above** can also be acquired via a new mutation

Question 30

What is the presentation of epidermolysis bullosa?

Answer 30

**Widespread blistering and skin shedding on slight handling of skin**

Question 31

What are the three types of epidermolysis bullosa, and which layers of the skin are affected?

Answer 31

**Simplex** - epidermis only **Junctional** - dermo-epidermal junction **Dystrophic** - all the way to the dermis

Question 32

How many faulty genes are involved in epidermolysis bullosa?

Answer 32

**\> 10 genes** (probably 20 now)

Question 33

The genes for which protein families are faulty in epidermolysis bullosa?

Answer 33

**Keratin** **Collagen** **Integrins**

Question 34

The faulty genes in epidermolysis bullosa are usually responsible for skin ____ and \_\_\_.

Answer 34

**structure** and **adhesion**

Question 35

What is **epidermolysis bullosa aquisita**?

Answer 35

**Rare autoimmune condition** similar to EB

Question 36

What is **haploinsufficiency**?

Answer 36

**Mutant gene** doesn't produce any protein, meaning only half as much protein is produced

Question 37

What is **dominant negative** disease expression?

Answer 37

**Mutant gene** causes production of abnormal protein, which interferes with normal protein

Question 38

A mutation in a gene for protein can cause that protein to gain new \_\_\_. Which disease type is this important in?

Answer 38

**function** **Cancer**

Question 39

If a disease is **autosomal recessive**, how much protein will be produced?

Answer 39

**None** oops

Question 40

How many generations are affected by **autosomal recessive** conditions?

Answer 40

**Usually only one**

Question 41

If a parent has an **autosomal recessive** condition, what is the chance of their child inheriting it?

Answer 41

**25%**

Question 42

The chance of children inheriting **autosomal recessive** conditions is increased in families which are \_\_\_.

Answer 42

**consanguineous** i.e inbreeding

Question 43

What is the name given to round, flat coffee-coloured marks on the skin which are asymptomatic?

Answer 43

**Cafe au lait macules**

Question 44

Cafe au lait macules are found on 10-20% of normal people. More than how many suggests that a person has a genetic disease?

Answer 44

**More than 5**

Question 45

What is a **neurofibroma**?

Answer 45

**Benign nerve sheath tumour found on the SKIN** - brown, soft, papular

Question 46

If a patient presents with more than 5 cafe au lait macules and neurofibromas, which genetic skin condition do they have?

Answer 46

**Neurofibromatosis type 1**

Question 47

What is the mode of inheritance of neurofibromatosis type I?

Answer 47

**Autosomal dominant**

Question 48

Apart from Cafe au lait macules and neurofibromas, what are some other signs of neurofibromatosis type I?

Answer 48

**Axillary / inguinal freckling** **Optic gliomas** (eye tumours) **Bony lesions**

Question 49

Which drugs may be used to treat neurofibromatosis type I in the future?

Answer 49

**MEK inhibitors**

Question 50

Most diseases **(are / aren't)** caused by one gene.

Answer 50

**aren't**

Question 51

Which skin disease, causing itchy skin and difficulty sleeping in infants, also has genetic contributing factors?

Answer 51

**Atopic eczema**

Question 52

A loss-of-function mutation in which gene is thought to cause atopic eczema?

Answer 52

**Filaggrin** gene

Question 53

Filaggrin mutations cause which disease?

Answer 53

**Ichthyosis vulgaris** dead skin cells don't shed, causing dry, itchy skin

Question 54

What is filaggrin an abbreviation for?

Answer 54

**Filament aggregating protein**

Question 55

The dark purple colour of which epidermal layer is lost in ichthyosis vulgaris?

Answer 55

**Granular layer**

Question 56

Mutations in the filaggrin gene increase your risk of which atopic conditions?

Answer 56

**Eczema** **Asthma** **Hayfever** **Peanut allergy**