Genetics

Question 1

Autosomal Dominant condition

Defn; Tips 2; Scenarios; Eg’s 6

Answer 1

1 gene is enough to develop the condition (ie. expressed as both heterozygous and homozygote states)

No gender discrepancy

Man not manifest clinically - non-penetrance

Scenarios:
1 parent has gene —> 50% chance child will have condition (50% not)
2 parents have gene —> 75% chance child will have condition (25% not)

HAEM VF

Huntington’s disease

Adult PKD

Ehlers-Danlos

Marfan’s

Von Willebrand’s

Familial hypercholesterolaemia

Question 2

Huntington’s

Onset; Sx 3; Rx

Answer 2

AD

Onset:
Usually between 30 and 50

Features:

1. Personality change (aggressive/irritable)
2. Chorea movements
3. Dementia

Treatment:
Symptomatic/depression

Question 3

Marfan’s

Def; Sx 3

Answer 3

AD

Connective tissue disorder

1. Limbs disproportionally long for trunk
2. Joint laxity
3. Cardiovascular features, e.g. mitral prolapse, aortic regurgitation

Question 4

Ehlers-Danlos

Def; Sx 3

Answer 4

AD

Abnormality of collagen production
—>

1. Joint laxity
2. Skin hyper-elasticity
3. Bruising

Question 5

Autosomal recessive

Def; Tips 3; Scenarios 2; Egs 6

Answer 5

= 2 genes needed to develop the condition (i.e. expressed only in homozygote state)

1 gene leads to ‘carrier’ status
No gender discrepancy
Little variability of expression

Scenarios:
1 parent w gene —> 0% child will have condition, 50% child will be carrier, 50% child will have nothing to do with condition

2 parents w gene —> 25% child has condition, 50% child carrier, 25% nothing

Egs: CHS PWT
Cystic fibrosis
Haemochromatosis
Sickle cell disease
PKU
Wilson’s disease
Thalassaemia

Question 6

Haemochromatosis

Def; Sx 4; Dx 2; Rx

Answer 6

AR

= accumulation of excess iron in organs
—>
1. Liver problems (cirrhosis)
2. Cardiac problems (failure, arrythmias)
3. Pancreatic problems (diabetes)
4. Joint problems (arthritis)

Dx:
1. High transferrin 2. High ferritin

Rx: Venesection

Question 7

Wilson’s disease

Def; Sx 3; Dx 3; Rx

Answer 7

= accumulation of excess copper in organs
—>
1. Liver problems (hepatitis, cirrhosis)
2. Neurological problems (tremor, dysarthria)
3. Renal problems (Fanconi’s syndrome)

Dx:

1. High serum FREE copper
2. Low TOTAL serum copper
3. Low caeruloplasmin

Rx: Copper chelating agents, e.g. pencillamine

Question 8

X-linked

M v F

Answer 8

Normally:

Female is XX (2 copies of X gene)

Male is XY (1 copy of X gene)

Question 9

X-linked recessive

Affects 2; Egs 3

Answer 9

MALES mainly affected…
…as one affected X will overshadow the Y

Rare in females…
…as need two affected Xs to cause the condition
(A normal X will override the affected X - remain a carrier)

Egs:
Haemophilia A/B
Duchenne
Red/green colour blindness

Question 10

X-linked dominant

Affects 2; Pos father; Egs 2

Answer 10

BOTH MALE & FEMALES affected (greater number of females)

Female affected if heterozygous (one gene affected) or homozygous (both genes affected)

Positive father —> give the condition to ALL daughters but NO sons

Egs: Fragile X, Rett’s