Large exonic deletions in POLR3B gene cause POLR3-related leukodystrophy

Orphanet J Rare Dis. 2015 Jun 5;10:69. doi: 10.1186/s13023-015-0279-9.


POLR3-related (or 4H) leukodystrophy is an autosomal recessive disorder caused by mutations in POLR3A or POLR3B and is characterized by neurological and non-neurological features. In a small proportion of patients, no mutation in either gene or only one mutation is found. Analysis of the POLR3B cDNA revealed a large deletion of exons 21-22 in one case and of exons 26-27 in another case. These are the first reports of long deletions causing POLR3-related leukodystrophy, suggesting that deletions and duplications in POLR3A or POLR3B should be investigated in patients with a compatible phenotype, especially if one pathogenic variant has been identified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Exons*
  • Female
  • Genes, Recessive
  • Hereditary Central Nervous System Demyelinating Diseases / genetics*
  • Humans
  • Infant
  • Male
  • RNA Polymerase III / genetics*
  • Sequence Deletion*


  • POLR3B protein, human
  • RNA Polymerase III