HSAN-VI: A spectrum disorder based on dystonin isoform expression

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Hereditary sensory and autonomic neuropathy type VI (HSAN-VI) is a rare genetic disorder.
• It is caused by mutations in the dystonin gene (DST).
• HSAN-VI was initially thought to be lethal in infancy, but milder forms exist.

Purpose of the Study:

• To investigate the role of dystonin isoforms in HSAN-VI heterogeneity.
• To understand the impact of DST mutations on disease presentation.

Main Methods:

• Analysis of human cases with DST mutations.
• Comparison with the mouse model dystonia musculorum (Dst).

Main Results:

• Loss of the neuronal dystonin-a2 isoform is a consistent feature in HSAN-VI.
• The severity of HSAN-VI may be modulated by compensatory mechanisms of other dystonin-a isoforms.

Conclusions:

• Dystonin-a2 deficiency is critical for HSAN-VI.
• Dystonin-a1 and dystonin-a3 may play roles in disease pathogenesis and severity.