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

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.