DNA Testing in Diagnosis of Movement Disorders

Question 1

What are the 3 possible effects of an unstable repeat expansion?

Answer 1

Non-coding repeats causing loss of function (impaired gene transcription)
Non-coding repeats conferring novel properties on RNA (toxic “gain-of-function”)
Repeats in a codon conferring novel properties on the affected protein (overrides function of normal protein)

Question 2

What is the main pathology in HD?

Answer 2

Abnormal polyQ-huntingtin product causes loss of medium spiny neurons in striatum of basal ganglia

Question 3

What is the genetic abnormality in Friedreich ataxia? What is the pathological process?

Answer 3

GAA repeat expansion in FXN gene

Causes mitochondrial iron accumulation leading to oxidative damage

Question 4

What is the affected range of repeats in Friedreich ataxia?

Answer 4

66-1700 repeats