Recessive mutations in POLR3B, encoding the second largest subunit of Pol III, cause a rare hypomyelinating leukodystrophy

Am J Hum Genet. 2011 Nov 11;89(5):652-5. doi: 10.1016/j.ajhg.2011.10.006. Epub 2011 Oct 27.


Mutations in POLR3A encoding the largest subunit of RNA polymerase III (Pol III) were found to be responsible for the majority of cases presenting with three clinically overlapping hypomyelinating leukodystrophy phenotypes. We uncovered in three cases without POLR3A mutation recessive mutations in POLR3B, which codes for the second largest subunit of Pol III. Mutations in genes coding for Pol III subunits are a major cause of childhood-onset hypomyelinating leukodystrophies with prominent cerebellar dysfunction, oligodontia, and hypogonadotropic hypogonadism.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cerebellum / pathology
  • Child
  • Codon, Nonsense / genetics*
  • Corpus Callosum / pathology
  • Genes, Recessive / genetics
  • Genetic Predisposition to Disease / genetics*
  • Hereditary Central Nervous System Demyelinating Diseases* / genetics
  • Hereditary Central Nervous System Demyelinating Diseases* / pathology
  • Humans
  • Models, Molecular
  • Mutation, Missense / genetics*
  • RNA Polymerase III / genetics*
  • Sequence Homology, Amino Acid


  • Codon, Nonsense
  • POLR3B protein, human
  • RNA Polymerase III