Week 1 - Genetics

Question 1

Which gene is involved in Hungtinton disease?

Answer 1

Huntingtin (HTT)

Question 2

How many CAG repeats in the Huntingtin gene is normal?

Answer 2

10-35

Question 3

How many CAG repeats in the Hungtintin gene are associated with Huntington’s disease?

Answer 3

36-120

Question 4

Which type of genetic transmission is susceptible to gene expansion during meiosis in Huntington disease?

Answer 4

Paternal

Question 5

What is genetic antisipation?

Answer 5

Expansion of gene mutation during meiosis, leading to increased severity and age on onset in subsequent generations

Question 6

How does a mutation in the huntingtin gene cause the symptoms of Huntington’s disease?

Answer 6

Gene codes for a polyglutamine tract

Expansion of tract causes insoluble protein aggregates which lead to neurotoxicity

Question 7

What are the main symptoms of myotonic dystrophy?

Answer 7

Progressive muscle weakness in early adulthood
Myotonia
Cataracts

Question 8

Which gene is mutation in myotonic dystrophy and what is the nature of the mutation?

Answer 8

DMPK gene

Unstable length mutation of CTG repeat in 3’ region (50 or more repeats)

Question 9

Which type of transmission more commonly causes expansion in myotonic dystrophy?

Answer 9

Maternal

Question 10

What effect does mutation of the DMPK gene have?

Answer 10

Indirect toxic effect upon spicing of other genes such as the chloride ion channel (causing myotonic)

Question 11

What is a common complication of CF? (other than lung infections)

Answer 11

Exocrine pancreas insufficiency

Question 12

How is CF diagnosed?

Answer 12

Screening of newborns (heel prick) by immunoreactive trypsin (IRT) level
DNA testing for CF mutations
Sweat testing for increased chloride concentration

Question 13

Which gene is mutation in CF?

Answer 13

CFTR

Question 14

What effect does a mutated CFTR gene have?

Answer 14

Defective chloride ion channel causing increased thickness of secretions

Question 15

What is the most common mutation in CF?

Answer 15

F508del

Question 16

What are the clinical features of NF1?

Answer 16

Cafe au lait macules
Neurofibromas
Short stature
Macrocephaly 
Learning difficulties

Question 17

Which conditions are patients with NF1 at increased risk of?

Answer 17

Hypertension
Scoliosis
Pathological tibial fractures
Tumours

Question 18

What type of inheritance is Duchenne Muscular Dystrophy?

Answer 18

X-linked recessive

Question 19

What type of inheritance is NF1?

Answer 19

Autosomal dominant

Question 20

What is the function of dystrophin?

Answer 20

Forms link between F-actin intracellularly and the dystroglycan complex

Question 21

What is creatine kinase?

Answer 21

Protein that leaks out of damaged muscle fibres into the blood

Question 22

What is often the first sign of DMD in boys on investigation?

Answer 22

High serum creatine kinase

Question 23

What is the difference between DMD and BMD?

Answer 23

Age of onset - 3 in DMD, 11 in BMD
Disability - wheelchair by 12y in DMD, much later in BMD
Deletion mutation - out of frame in DMD, in frame BMD

Question 24

By what manner is fragile X syndrome inherited?

Answer 24

X-linked recessive

Question 25

What causes genetic anticipation in Fragile X Dyndrome?

Answer 25

Repeats in the 5' region of FMR1 gene

Question 26

What is the consequence of an expansion >200 repeats in the FMR1 gene? (Fragile X)

Answer 26

Severe phenotype in males | Carrier females mildly affected

Question 27

What are the complications of Down syndrome?

Answer 27

Learning difficulties Heart malformations Hypothyroidism

Question 28

What is Edwards Syndrome?

Answer 28

Trisomy 18

Question 29

What are the clinical features of Edwards Syndrome?

Answer 29

Small chin Clenched hands Malformations of heart and kidney Profound learning difficulty

Question 30

What is Patau Syndrome?

Answer 30

Trisomy 13

Question 31

What are the clinical features of Patau syndrome?

Answer 31

``` Cleft palate Microphthalmia Abnormal ears Clenched firsts Extra little finger ```

Question 32

At what stage in fertilisation is PGD performed?

Answer 32

Day 3 when embryo 6-10 cells

Question 33

What are the cons of PIGD?

Answer 33

Long wait Not available to all women Multiple visits and procedures Take home baby rate around 50% per cycle

Question 34

What conditions is embryo sexing used to prevent?

Answer 34

X-linked recessive

Question 35

How do you calculate the sensitivity of a screening test?

Answer 35

TP/(TP+FN)

Question 36

How do you calculate the specificity of a screening test?

Answer 36

TN/(FP+TN)

Question 37

What is used to screen for DS in 1st trimester?

Answer 37

Combined Ultrasound and Biochemical Screening (CUBS)

Question 38

What does CUB consist of?

Answer 38

Maternal blood biochemical markers Ultrasound looking for increased nuchal translucency

Question 39

Give examples of conditions that can be screened for in neonates by the heel-prick test

Answer 39

``` Phenylketonuria MCADD Congenital hypothyroidism CF Sickle cell disorder ```

Question 40

Name a disease that is screened for in Jewish people

Answer 40

Tay Sachs

Question 41

Name 2 invasive prenatal screening tests

Answer 41

Chorionic villous sampling | Amniocentesis

Question 42

What is NIPT?

Answer 42

Non-invasive prenatal testing on maternal plasma for free fetal DNA

Question 43

What is NIPT used for?

Answer 43

Sex determination in X linked conditions Paternal mutations e.g. FGFR3 Aneuploidy

Question 44

What condition is ivacaftor used to treat?

Answer 44

CF

Question 45

Which mutation must a patient have to receive ivacaftor?

Answer 45

G551D

Question 46

What is the function of ivacaftor?

Answer 46

Mutation blocks the opening of CFTR chloride ion channels Ivacaftor reopens the channel

Question 47

Which drug is used to treat lung cancer with a EGFR mutation and what is it's mechanism?

Answer 47

Gefitinib Tyrosine kinase inhibitor

Question 48

Which drug is used to treat HER2 positive breast cancer?

Answer 48

Trastuzumab (Herceptin)

Question 49

Describe a possible future therapy for DMD

Answer 49

Use exon skipping to convert DMD to BMD phenotype by altering the splicing patterns to correct the reading frame

Question 50

Name 2a drugs that may be used in DMD

Answer 50

Ataluren