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.
BMC medical genetics [electronic resource]
Chromosomal Instability; DNA Breaks; DNA Polymerase II; Exome; Female; Homozygote; Humans; Infant; Infant, Newborn; Mutation; Poly-ADP-Ribose Binding Proteins; Pregnancy
POLE1, FILS syndrome, Immunodeficiency, Dysmorphism, Primordial dwarfism
Thiffault, I., Saunders, C., Jenkins, J., Raje, N., Canty, K., Sharma, M., Grote, L., Welsh, H. I., Farrow, E., Twist, G., Miller, N., Zwick, D., Zellmer, L., Kingsmore, S. F., Safina, N. P. A patient with polymerase E1 deficiency (POLE1): clinical features and overlap with DNA breakage/instability syndromes. BMC medical genetics [electronic resource] 16, 31-31 (2015).