genetics: predisposition to adult onset disease

Question 1

why are adults referred to genetics?

Answer 1

diagnosis

testing: predicitve, carrier, cascade screening
history: family history, foetal loss or recurrent miscarriages

Question 2

mechanisms of adult onset genetic disease

Answer 2

single gene

chromosomal

mitochondrial

multifactorial

Question 3

what conditions make risk estimation easier?

Answer 3

single gene disorders with high penetrance

Question 4

what is the impact of multifactorial conditions?

Answer 4

risk estimation is more difficult

polygenic genetic component interacting with environmental factors

Question 5

principles of ethics in medicine

Answer 5

autonomy

beneficence

non-maleficence

justice

Question 6

what are the rules regarding predictive tests?

Answer 6

prevention or treatment

uncertainty: adequate information about uncertainty

counselling

medical benefits: in children/adolscents

privacy: third parties (employers, insurers) should have no access

Question 7

what is the implication of shared genetic heritage?

Answer 7

genetic disease affects families, not individuals

discovery of a genetic disorder implies a risk for relatives

Question 8

amyotrophic lateral sclerosis (motor neurone disease)

Answer 8

aMyotrophic Lateral SClerosis

• muscle weakness: wasting, increased reflexes
• Lateral corticospinal tract: limb and bulbar muscles involved
• signs: purely motor (fasciculations)
• cognition spared

Question 9

what is the gene involved in ALS

Answer 9

Cu/ZN superoxide dismutase (SOD gene)

enzyme is expressed highly in motor neurones

Question 10

what does superoxide dismutase (SOD) do

Answer 10

protects cells from free radical damage and progressive cell degradation:

• ageing
• ischaemic tissue damage
• DNA damage
• lipid peroxidation
• ionising radiation damage
• protein denaturation

catalyses the conversion of intracellular superoxide radicals produced during normal metabolism

Question 11

what are the 3 forms of SOD present in humans?

Answer 11

SOD1: cytoplasm, contains copper and zinc, on chromosome 21

SOD2: mitochondria, contains manganese in its reactive core, on chromosome 6

SOD3: extracellular, contains copper and zinc, on chromosome 4

Question 12

what is the penetrance of ALS?

Answer 12

incomplete penetrance

no certainty even with mutation analysis

no cure

Question 13

describe X-lined inheritance

Answer 13

males are affected in more than one generation

no affected females

no male to male transmissin seen
- affected males are linked through unaffected females

Question 14

huntington’s disease

Answer 14

autosomal dominant (unique mutation - CAG expression)

onset: 30 - 40 years, 15 - 20 years duration, not curable

fully penetrant

clinical features
- movement disorder: chorea, athetosis, myoclonus, rigidity

• cognitive changes: poor planning and memory, subcortical dementia (EF)
• personality change: irritable, apathetic, disinhibited, self centred