POLR1C variants and pathophysiology of hypomyelinating leukodystrophy

Takeaway

  • The broad clinical spectrum of RNA polymerase III-related leukodystrophy (Pol III-RLD) is confirmed by the absence of characteristic findings in the current, novel POLR1C variant-expressing familial group.

Why this matters

  • Pol III-RLD is a rare disorder characterized by CNS hypomyelination and corpus callosal atrophy, with clinical manifestations including cerebellar ataxia, hypodontia and hypogonadism; caused by pathogenic variants in the Pol III subunits POLR3A and POLR3B, and more recently, in POLR1C in patients negative for the previous two.

  • The identification of a novel causative variant for Pol III-RLD is important for enhancing understanding of its pathogenesis, with a view to encourage further research and eventual development of more efficient, targeted treatments to improve patient outcomes.