Genetics

Question 1

What is the difference between a somatic mutation and a germline mutation?

Answer 1

Somatic mutation affects one cell in non-germline tissues and are non-heritable
Germline mutation affects cell in egg or sperm and is passed onto every cell in offspring, causing family cancer syndromes

Question 2

What is an example of oncogenic cancer.

Answer 2

Oncogene ABL fuses sporadically with BCR, making BCR-ABL fusion protein and causes leukaemia

Question 3

What is HNPCC?

Answer 3

Hereditary non-polyposis colorectal cancer
Mutation in mismatch repair genes
Adenoma-carcinoma sequence for polyp formation
AKA Lynch syndrome

Question 4

Where do HNPCC tumours usually present?

Answer 4

Proximal colon

Often endometrial cancers for women

Question 5

What are some options for breast surveillance?

Answer 5

Breast awareness
Annual or clinical exam
Mammography
MR screening for highest risk

Question 6

What are the main genes tested for in breast cancer?

Answer 6

BRCA1
BRCA2
PALB2
PTEN
P53
CHEK2

Question 7

What are the main genes tested for in ovarian cancer?

Answer 7

BRCA1
BRCA2
Lynch genes
RAD51C
RAD51D

Question 8

What is a management option for BRCA1/2 carriers?

Answer 8

Prophylactic mastectomy

Significantly reduces risk

Question 9

What are some drawbacks of prophylactic oophererctomy for primary ovarian cancer?

Answer 9

Peritoneal carcinomatosis may still occur

Induces surgical menopause

Question 10

What are some options for surveillance of CRC?

Answer 10

Colonoscopy (Frequency depends on risk)

Prophylactic aspirin

Question 11

What are some risks of genetic testing for familial cancers?

Answer 11

Does not detect all mutations
Continued risk of sporadic cancer
Efficacy of interventions variable
May result in psychosocial or economic harm

Question 12

What are the 3 ways multi-system disorders can be inherited?

Answer 12

Chromosomal (Trisomy 21)
Single gene disorders (myotonic dystrophy, CF, Duchenne’s)
Multifactorial (diabetes)

Question 13

Why do some mutations give multi-system disorders?

Answer 13

Single genes may have diverse functions
Single gene widely expressed in different tissues
Gene may be tissue specific but tissue is in many different systems

Question 14

How does neurofibromatosis type 1 (NF1) present?

Answer 14

Cafe au lait spots
Neurofibromas
Axillary freckling
Lisch nodes
Optic glioma
Thinning of long bone cortex
Raised BP

Question 15

Which gene causes NF1?

Answer 15

17q

Question 16

What are the main features of NF2?

Answer 16

Acoustic neuroma
CNS and spinal tumour
CAL spots
NF2 gene is on chromosome 22

Question 17

What is the classic triad of Tuberous Sclerosis (TS)?

Answer 17

Epilepsy
Learning difficulty
Skin lesions

Myoclonic seizures

Question 18

Which genes cause TS?

Answer 18

TSC1

TSC2

Question 19

How are relatives at risk of TS screened?

Answer 19

Skin signs
Retinal exam
Cranial MR scan
Renal USS
Echocardiogram

Question 20

How does myotonic dystrophy present?

Answer 20

Bilateral late-onset cataract
Muscle weakness
Stiffness
Myotonia
Low motivation
Bowel problems
Heart block

Question 21

Why may an adult be referred for pre-symptomatic testing?

Answer 21

Diagnosis
Predictive testing
Carrier testing
Family history
Fetal loss or recurrent miscarriage

Question 22

Is risk estimation more difficult for single gene or multifactorial conditions?

Answer 22

Single gene

Especially those with high penetrance

Question 23

What is a requirement of testing for children and adolescents?

Answer 23

Must be some potential medical benefits

Question 24

What is mean age onset for MND?

Answer 24

55

Question 25

What are some clinical features of MND?

Answer 25

Progressive muscle weakness, wasting and increased reflexes Pure motors signs with fasciculations Cognition spared Death due to respiratory failure

Question 26

What is another name for MND?

Answer 26

Amyotrophic lateral sclerosis

Question 27

What happens in MND?

Answer 27

Superoxide Dismutase | Catalysis of conversion of intracellular superoxide radicals

Question 28

Is Huntington's disease usually youth or adult onset?

Answer 28

Adult

Question 29

How does HD affect movement?

Answer 29

Chorea Athetosis Myoclonus Rigidity

Question 30

How does HD affect cognitive changes?

Answer 30

``` Poor planning and memory Subcortical dementia (executive function) ```

Question 31

How does HD affect personality?

Answer 31

``` Irritable Apathetic Loss of empathy Disinhibition Self centred ```

Question 32

How does HD affect psychiatry?

Answer 32

Depression Paranoia Psychosis

Question 33

What are some disadvantages of a positive predictive test?

Answer 33

Less hope Still uncertain with onset Risk to offspring Potential insurance/mortgage problems

Question 34

What are some advantages of a positive predictive test?

Answer 34

Uncertainty removed Make plans for future Arrange surveillance Inform children or decide whether or not to have them

Question 35

What are some requirements for predictive testing?

Answer 35

Info must be useable for prevention or treatment Require proper counselling Children only tested if potential medical benefits Third parties should have no access Susceptibility testing requires adequate information about uncertainty

Question 36

What are some common features of down's syndrome?

Answer 36

``` Flattened face Almond shaped slanted eyes Short neck Small ears, hands and feet White spots in iris Tongue sticks out Single palmar crease Curved pinkies towards thumb Poor muscle tone Short Small malleolus ```

Question 37

What are the main characteristics of Kallman syndrome?

Answer 37

Delayed or absent puberty | Impaired sense of smell