Genetics

Question 1

What is the biggest determinant of the number of new mutations in a child?

Answer 1

Paternal age

Question 2

What causes tuberous sclerosis?

Answer 2

Autosomal dominant inherited disease, mutations in genes that code for tubers and hamartin are suppressors genes that show heterogeneity (mutation can be either gene)

Question 3

How does tuberous sclerosis present?

Answer 3

Infantile seizures, periungunal fibromata, longitudinal ridging, ash leaf macules (visible under Woods lamp), shagreen patches, enamel pitting

Question 4

Describe the tumours that can arise as a result of tuberous sclerosis

Answer 4

• periungual fibromas on nails
• fascial angiofibromas (papular lesions)
• hamartomas - angiomyolipoma on heart, lungs, kidneys
• cortical tubers (brain) +/- calcification leads to seizures

Question 5

How is tuberous sclerosis treated?

Answer 5

MTOR inhibitor acts further down the pathway to inhibit further cell growth

Question 6

What is epidermolysis bullosa?

Answer 6

Genetic skin fragility condition due to loss of adhesion between skin cells

Question 7

What causes epidermolysis bullosa?

Answer 7

Autosomal dominant, recessive, new mutation or acquired - involves more than 10 genes all linked to skin structure and adhesion

Question 8

How does epidermolysis bullosa present?

Answer 8

Widespread blistering and loss of skin, common in new borns

Question 9

What is the treatment for epidermolysis bullosa?

Answer 9

RNA based therapies

Question 10

Name the three types of epidermolysis bullosa

Answer 10

• EB simple (cells in epidermis top sticking together)
• EB junctional (dermo-epidermal junction)
• EB dystrophic (cells in dermis)

Question 11

Define haploinsufficiency

Answer 11

A mutation to one copy of a gene results in less protein being produced, it is not sufficient for a normal phenotype

Question 12

Define dominant negative disease

Answer 12

Mutant allele produces an abnormal peptide which interferes with the normal function

Question 13

Define complete loss of protein due to mutation

Answer 13

Autosomal recessive two faulty copies of the gene causes no protein to be produced

Question 14

What causes neurofibromatosis?

Answer 14

Mutation to NF1 gene in RAS/RAF pathway which is involved in the formation of transcription factors and cell growth

Question 15

How does neurofibromatosis present?

Answer 15

Café au lait macules (more than 5 bigger than 1cm)
Neurofibromas (soft rubbery & dimple down on touch)
Plexiform neuroma, axillary/inguinal freckling. optic glioma, lisch nodules in eyes, distinctive bony lesion

Question 16

What is the treatment for neurofibromatosis?

Answer 16

MEK inhibitors