Gene variants linked to planned nerve fiber breakdown in human diseases

Pathogenic variants in four key genes are linked to severe neurodegenerative conditions.

• Variants in NAMPT are associated with sensory and motor neuropathy along with neurodevelopmental symptoms.
• NMNAT1 variants are known to cause Leber Congenital Amaurosis type 9.
• Childhood-onset peripheral neuropathies have been linked to NMNAT2 variants.
• Gain-of-function variants in SARM1, which have active NAD-depleting activity, are found more frequently in amyotrophic lateral sclerosis patients.
• Disruption of NAD homeostasis is essential for axon survival, with genetic variants leading to various neurodegenerative outcomes.

Simplified