HMSN/HNPP

Question 1

Clinical features of HMSN1

Answer 1

distal muscle weakness
pes cavus
frequent trips, falls
difficulty walking on uneven surfaces
muscle wastage in calves (inverted champagne bottle)

Question 2

Molecular pathogenesis of PMP22 and disease

Answer 2

PMP22 expressed by Schwann cells of peripheral nerves - produces 2-5% of total myelin

PMP22 dup causes increases PMP22 expression > disrupts regulation of myelin production > demyelination of peripheral nerves > abnormal axon function > reduced nerve conduction speeds and axonal loss

PMP22 del > Reduced myelin > disruption of myelin junctions > impaired propogation of nerve potentials

Question 3

What does HMSN stand for?

Answer 3

Hereditary motor and sensory neuropathy

Question 4

Chromosome location for PMP22

Answer 4

17p12

Question 5

Cause HNPP

Answer 5

85% caused by PMP22 deletions

15% caused by LOF mutations in PMP22

Question 6

Cause HMSN

Answer 6

???

Question 7

Clinical features of HNPP

Answer 7

transient recurrent episodes of focal weakness and sensory loss- usually caused by pressure or injury

Question 8

Why do PMP22 deletions and duplications occur?

Answer 8

PMP22 gene flanked by repeat regions; CMT1A-REP

NAHR between these regions leads to recurrent dels/dups