Non-Cancer Genetic Conditions

Question 1

What is the typical age of onset of huntington’s disease?

Answer 1

30-50 years

Question 2

What gene is mutated in Huntington’s disease?

Answer 2

Huntingtin

Question 3

What are the symptoms of Huntington’s disease?

Answer 3

Chorea (involuntary movements)
Dementia
Psychiatric symptoms

Question 4

Huntington’s disease exhibits genetic anticipation. The repeat sequence responsible for this is more likely to expand if the mutation is inherited from which parent?

Answer 4

Father

Question 5

Myotonic dystrophy disease exhibits genetic anticipation. The repeat sequence responsible for this is more likely to expand if the mutation is inherited from which parent?

Answer 5

Mother

Question 6

Up to how many repeats of the mutation can a person have before becoming affected by Huntington’s disease?

Answer 6

35

Question 7

Where in the gene is the CAG repeat which causes Huntington’s disease present?

Answer 7

Coding sequence

Question 8

What is the normal product of the Huntingtin gene?

Answer 8

A polyglutamine tract

Question 9

The polyglutamine tract which is normally coding for by the huntington gene is expanded in Huntington’s disease. How does this result in the symptoms seen in this condition?

Answer 9

The expanded polyglutamine tract forms an insoluble protein aggregate which causes neurotoxicity

Question 10

There is a cure for Huntington’s disease. T/F?

Answer 10

False

Question 11

Under what conditions can testing of an unaffected relative for Huntington’s disease be performed?

Answer 11

After full discussion of pros and cons

With full written consent

Question 12

What are the symptoms of myotonic dystrophy?

Answer 12

Progressive muscle weakness in early adulthood
Myotonia
Cataracts

Question 13

Myotonic dystrophy results from an unstable length mutation due to a repeat of which three bases?

Answer 13

CTG

Question 14

The mutation which causes myotonic dystrophy is not a part of the coding sequence. How does it exhibit is affect?

Answer 14

It has an indirect toxic effect upon the splicing of other genes such as the CLCN1 gene for the chloride ion channel

Question 15

Where in the DMPK gene is the mutation responsible for myotonic dystrophy present?

Answer 15

The 3’ end, downstream from the coding sequence

Question 16

On which gene is the mutation responsible for myotonic dystrophy present?

Answer 16

DMPK gene

Question 17

How many CTG repeats are required before a person becomes affected by myotonic dystrophy?

Answer 17

50 or more

Question 18

Myotonic dystrophy can cause increased risks for general anaesthesia and an increased risk of diabetes mellitus. T/F?

Answer 18

True

Question 19

What is the most common life limiting autosomal recessive condition in caucasians?

Answer 19

Cystic fibrosis

Question 20

What symptoms/complications are caused by cystic fibrosis?

Answer 20

Recurrent lung infections
Exocrine pancreatic insufficiency
Male infertility

Question 21

What is the carrier frequency for cystic firbosis?

Answer 21

1/20 to 1/25

Question 22

How are newborns screened for cystic fibrosis?

Answer 22

By testing the immunoreactive trypsin level

Question 23

If a newborn has a positive screening test for cystic fibrosis, how is the diagnosis confirmed?

Answer 23

By DNA testing for CF mutations

Sweat testing for increased chloride concentrations

Question 24

Cystic fibrosis is the result of mutation in which gene?

Answer 24

CFTR gene

Question 25

What is the most common mutation which causes cystic fibrosis?

Answer 25

F508del - a in-frame deletion of one codon resulting in a loss of phenylalanine at position 508 and preventing normal protein folding and insertion in the plasma membrane

Question 26

What are the signs and symptoms of neurofibromatosis type 1?

Answer 26

Cafe au lait macules (coffee coloured patches on the skin) Neurofibromas Short stature Macropcephaly

Question 27

Neurofibromatosis type 1 can cause learning difficulties in a small percentage of people. T/F?

Answer 27

True

Question 28

On examination of the eyes with a slit lamp, what will be seen in patients with neurofibromatosis type 1?

Answer 28

2 or more lisch nodules

Question 29

What complications/conditions are patients with neurofibromatosis type 1 at increased risk of?

Answer 29

Hypertension Scoliosis requiring surgery Pathological tibial fractures Significant tumours such as phaechromocytomas, sarcomas ad optic pathway gliomas

Question 30

Patients wit neurofibromatosis require annual follow-up. T/F?

Answer 30

True

Question 31

What is the normal role of dystrophin (the protein which is mutated in DMD and BMD)?

Answer 31

To form a link between F actin intracellularly and the dystroglycan complex on the cell surface

Question 32

Becker's muscular dystrophy is more severe than duchenne's. T/F?

Answer 32

False - the opposite is true

Question 33

At birth. before any symptoms are noticable, serum creatinine kinase will be massively elevated in individuals with BMD and DMD. Why is this?

Answer 33

Creatine kinase will leak out of damaged muscle fibres in the serum

Question 34

Why is duchenne's muscular dystrophy more severe than Becker's muscular dystrophy?

Answer 34

Because DMD is usually caused by out of reading frame mutations where BMD is usually caused by in reading frame mutations

Question 35

What is the typical age of onset of duchenne's muscular dystrophy?

Answer 35

3 years

Question 36

What is the typical age of onset of becker's muscular dystrophy?

Answer 36

11 years

Question 37

At what age will patients with duchenne's muscular dystrophy typically require a wheelchair?

Answer 37

Approx. 12 years

Question 38

Fragile x syndrome is caused by mutations in which gene?

Answer 38

FMR1

Question 39

In which region of the FRM1 gene do mutations causing fragile x syndrome occur?

Answer 39

Promoter sequences

Question 40

How does a mutation in the promoter region of the FRM1 gene result in fragile x syndrome?

Answer 40

By causes DNA methylation which switches off the gene inappropriately

Question 41

What is the most common cause of inherited learning disability?

Answer 41

Fragile X syndrome

Question 42

How many repeats are typically required for an individual to be affected by fragile x syndrome?

Answer 42

>200 repeats

Question 43

What chromosome abnormality results in Edward's syndrome?

Answer 43

Trisomy 18

Question 44

What chromosome abnormality results in Patau syndrome?

Answer 44

Trisomy 13

Question 45

What are the signs and symptoms of Edward's syndrome?

Answer 45

Small chin Clenched hands with overlapping fingers Malformations of the heart, kidneys and other organs

Question 46

50% of babies born with Patau syndrome will die within the first month. T/F?

Answer 46

True

Question 47

If babies born with Patau or Eward's syndrome survive their first year, they will have profound learning disabilities. T/F?

Answer 47

True

Question 48

What are the signs and symptoms of Patau syndrome?

Answer 48

``` Cleft lip and palate Micropthalmia Abnormal ears Clenched fists Post-axial polydactyly (an extra pinky) ```

Question 49

What is the most common cause of trisomies?

Answer 49

Maternal non dysjunction - failure of the normal separation of the two chromosomes in meiosis

Question 50

The risk of trisomies increases with maternal age. T/F?

Answer 50

True