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].

PMID: 25948378 DOI: 10.1186/s12881-015-0177-y

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.

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