Channelopathies

Question 1

What mutation causes hypOkalemic periodic paralysis? What is the function of the protein?

Answer 1

Mutation in CACNA1s; α1- subunit of the dihydropyridine-sensitive L-type VGCC found in skeletal muscle. This channel functions as the voltage sensor of the ryanodine receptor

Question 2

What 2 conditions can be caused by CACNA1S mutations?

Answer 2

1. HypOkalemic periodic paralysis
2. Malignant hyperthermia (rarely; more common cause is RYR)

Question 3

What mutation causes hypERkalemic periodic paralysis? What is its inheritance?

Answer 3

• autosomal dominant disorder
• SCN4A mutation

Question 4

What conditions are caused by SCN4A mutations?

Answer 4

1. HyperKPP
2. (Rarely hypOkpp)
3. Paramyotonia congenita
4. potassium aggravated myotonia

Question 5

Differentiate hypOkpp from hypERkpp

Answer 5

Question 6

What diseases are caused by RYR1 mutations?

Answer 6

• Malignant hyperthermia
• Central core disease

Question 7

The most common mutation causing congenital myasthenic syndromes is:

Answer 7

mutations affecting nicotinic acetylcholine receptor

Question 8

Which 3 diseases can be caused by CACNA1A mutations

Answer 8

1. Familial hemiplegic migraine
2. Episodic ataxia type 2
3. SCA6

Question 9

Which gene is mutated in paramyotonia congenita?

Answer 9

SCN4A

Question 10

Which gene is mutated in myotonia congenita?

Answer 10

CLCN1