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

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

Thiffault I1,2, Saunders C3,4,5, Jenkins J6,7,8, Raje N9, Canty K10, Sharma M11, Grote L12,13,14, Welsh HI15,16,17, Farrow E18, Twist G19, Miller N20, Zwick D21, Zellmer L22, Kingsmore SF23,24,25,26, Safina NP27,28,29.

Author information

1
Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. ithiffault@cmh.edu.
2
Department of Pathology and Laboratory Medicine, Childrens Mercy Hospitals, Kansas City, MO, 64108, USA. ithiffault@cmh.edu.
3
Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. csaunders@cmh.edu.
4
Department of Pathology and Laboratory Medicine, Childrens Mercy Hospitals, Kansas City, MO, 64108, USA. csaunders@cmh.edu.
5
University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. csaunders@cmh.edu.
6
Division of Clinical Genetics, Childrens Mercy Hospital, 2420 Pershing Road, Suite 421, Kansas City, MO, 64108, USA. jljenkins@cmh.edu.
7
Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. jljenkins@cmh.edu.
8
University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. jljenkins@cmh.edu.
9
Pediatric Allergy, Asthma and Immunology Clinic, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. nraje@cmh.edu.
10
Dermatology Clinic, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. kmcanty@cmh.edu.
11
Department of Hematology and Oncology, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. msharma@cmh.edu.
12
Division of Clinical Genetics, Childrens Mercy Hospital, 2420 Pershing Road, Suite 421, Kansas City, MO, 64108, USA. lgrote@cmh.edu.
13
Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. lgrote@cmh.edu.
14
University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. lgrote@cmh.edu.
15
Division of Clinical Genetics, Childrens Mercy Hospital, 2420 Pershing Road, Suite 421, Kansas City, MO, 64108, USA. hwelsh@cmh.edu.
16
Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. hwelsh@cmh.edu.
17
University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. hwelsh@cmh.edu.
18
Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. egfarrow@cmh.edu.
19
Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. gtwist@cmh.edu.
20
Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. nmiller@cmh.edu.
21
Department of Pathology and Laboratory Medicine, Childrens Mercy Hospitals, Kansas City, MO, 64108, USA. dzwick58@gmail.com.
22
Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. lazellmer@cmh.edu.
23
Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. sfkingsmore@cmh.edu.
24
Department of Pathology and Laboratory Medicine, Childrens Mercy Hospitals, Kansas City, MO, 64108, USA. sfkingsmore@cmh.edu.
25
Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. sfkingsmore@cmh.edu.
26
University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. sfkingsmore@cmh.edu.
27
Division of Clinical Genetics, Childrens Mercy Hospital, 2420 Pershing Road, Suite 421, Kansas City, MO, 64108, USA. nsafina@cmh.edu.
28
Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. nsafina@cmh.edu.
29
University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. nsafina@cmh.edu.

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.

PMID:
25948378
PMCID:
PMC4630961
DOI:
10.1186/s12881-015-0177-y
[Indexed for MEDLINE]
Free PMC Article

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