A patient with polymerase E1 deficiency (POLE1): clinical features and overlap with DNA breakage/instability syndromes PMID: 25948378

ADC Targets in Oncology

2026-04-10

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.

Isabelle Thiffault ¹ ² , Carol Saunders ³ ⁴ ⁵ , Janda Jenkins ⁶ ⁷ ⁸ , Nikita Raje ⁹ , Kristi Canty ¹⁰ , Mukta Sharma ¹¹ , Lauren Grote ¹² ¹³ ¹⁴ , Holly I Welsh ¹⁵ ¹⁶ ¹⁷ , Emily Farrow ¹⁸ , Greyson Twist ¹⁹ , Neil Miller ²⁰ , David Zwick ²¹ , Lee Zellmer ²² , Stephen F Kingsmore ²³ ²⁴ ²⁵ ²⁶ , Nicole P Safina ²⁷ ²⁸ ²⁹

Affiliations

1. Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. [email protected].
2. Department of Pathology and Laboratory Medicine, Childrens Mercy Hospitals, Kansas City, MO, 64108, USA. [email protected].
3. Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. [email protected].
4. Department of Pathology and Laboratory Medicine, Childrens Mercy Hospitals, Kansas City, MO, 64108, USA. [email protected].
5. University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. [email protected].
6. Division of Clinical Genetics, Childrens Mercy Hospital, 2420 Pershing Road, Suite 421, Kansas City, MO, 64108, USA. [email protected].
7. Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. [email protected].
8. University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. [email protected].
9. Pediatric Allergy, Asthma and Immunology Clinic, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. [email protected].
10. Dermatology Clinic, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. [email protected].
11. Department of Hematology and Oncology, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. [email protected].
12. Division of Clinical Genetics, Childrens Mercy Hospital, 2420 Pershing Road, Suite 421, Kansas City, MO, 64108, USA. [email protected].
13. Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. [email protected].
14. University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. [email protected].
15. Division of Clinical Genetics, Childrens Mercy Hospital, 2420 Pershing Road, Suite 421, Kansas City, MO, 64108, USA. [email protected].
16. Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. [email protected].
17. University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. [email protected].
18. Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. [email protected].
19. Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. [email protected].
20. Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. [email protected].
21. Department of Pathology and Laboratory Medicine, Childrens Mercy Hospitals, Kansas City, MO, 64108, USA. [email protected].
22. Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. [email protected].
23. Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. [email protected].
24. Department of Pathology and Laboratory Medicine, Childrens Mercy Hospitals, Kansas City, MO, 64108, USA. [email protected].
25. Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. [email protected].
26. University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. [email protected].
27. Division of Clinical Genetics, Childrens Mercy Hospital, 2420 Pershing Road, Suite 421, Kansas City, MO, 64108, USA. [email protected].
28. Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. [email protected].
29. University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. [email protected].

Abstract

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.