Novel mutations in TSEN54 in pontocerebellar hypoplasia type 2

J Child Neurol. 2014 Apr;29(4):520-5. doi: 10.1177/0883073812470002. Epub 2013 Jan 9.


Pontocerebellar hypoplasias represent a group of neurodegenerative autosomal recessive disorders characterized by hypoplasia/atrophy of the cerebellum, hypoplastic ventral pons, and microcephaly and associated with various clinical features. Pontocerebellar hypolasia type 2 is the most common form, and different mutations in genes encoding subunits of the transfer ribonucleic acid (RNA)-splicing endonuclease (TSEN) complex were identified in patients. The authors report clinical, imaging, and molecular studies in 2 unrelated patients with different clinical pictures of the pontocerebellar hypoplasia type 2 spectrum and novel mutations in TSEN54, aiming to further define the clinical spectrum of the disease and possible indicators of more favorable progression. They identified a novel missense mutation c.355T>G/p.Y119D in compound heterozygosity with the "common" c.919G>T/p.A307S (patient 1) and a novel homozygous c.7ins6(CCGGAG)/p.E2-P3insPE variant (patient 2). An expanded array of mutations might contribute in defining possible differences in severity and phenotype-genotype correlations.

Keywords: TSEN54 gene; genotype-phenotype correlation; microcephaly; modeling; novel mutations; pontocerebellar hypoplasia.

Publication types

  • Case Reports

MeSH terms

  • Brain / pathology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Endoribonucleases / genetics*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mutation / genetics*
  • Olivopontocerebellar Atrophies / diagnosis
  • Olivopontocerebellar Atrophies / genetics*


  • Endoribonucleases
  • TSEN54 protein, human

Supplementary concepts

  • Pontocerebellar Hypoplasia Type 2