A patient with polymerase E1 deficiency (POLE1): clinical features and overlap with DNA breakage/instability syndromes

BMC Med Genet. 2015 May 7;16:31. doi: 10.1186/s12881-015-0177-y.


Background: Chromosome instability syndromes are a group of inherited conditions associated with chromosomal instability and breakage, often leading to immunodeficiency, growth retardation and increased risk of malignancy.

Case presentation: We performed exome sequencing on a girl with a suspected chromosome instability syndrome that manifested as growth retardation, microcephaly, developmental delay, dysmorphic features, poikiloderma, immune deficiency with pancytopenia, and myelodysplasia. She was homozygous for a previously reported splice variant, c.4444 + 3A > G in the POLE1 gene, which encodes the catalytic subunit of DNA polymerase E.

Conclusion: This is the second family with POLE1-deficency, with the affected individual demonstrating a more severe phenotype than previously described.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomal Instability / genetics*
  • DNA Breaks*
  • DNA Polymerase II / deficiency*
  • DNA Polymerase II / genetics*
  • Exome / genetics
  • Female
  • Homozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Mutation
  • Poly-ADP-Ribose Binding Proteins
  • Pregnancy


  • Poly-ADP-Ribose Binding Proteins
  • DNA Polymerase II
  • POLE protein, human