tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia

Nat Genet. 2008 Sep;40(9):1113-8. doi: 10.1038/ng.204.


Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / metabolism
  • Cerebellum / abnormalities*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 17
  • Endoribonucleases / genetics*
  • Humans
  • Models, Molecular
  • Mutation*
  • Polymorphism, Single Nucleotide
  • Pons / abnormalities*
  • Syndrome


  • Endoribonucleases
  • splicing endonuclease