title: A patient with polymerase E1 deficiency (POLE1): clinical features and overlap with DNA breakage/instability syndromes.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  This is the second family with POLE1-deficency, with the affected individual demonstrating a more severe phenotype than previously described.
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. ithiffault@cmh.edu.|Department of Pathology and Laboratory Medicine, Childrens Mercy Hospitals, Kansas City, MO, 64108, USA. ithiffault@cmh.edu.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Thiffault
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. csaunders@cmh.edu.|Department of Pathology and Laboratory Medicine, Childrens Mercy Hospitals, Kansas City, MO, 64108, USA. csaunders@cmh.edu.|University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. csaunders@cmh.edu.
authors.forename: Carol
authors.initials: C
authors.lastname: Saunders
authors.affiliation: Division of Clinical Genetics, Childrens Mercy Hospital, 2420 Pershing Road, Suite 421, Kansas City, MO, 64108, USA. jljenkins@cmh.edu.|Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. jljenkins@cmh.edu.|University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. jljenkins@cmh.edu.
authors.forename: Janda
authors.initials: J
authors.lastname: Jenkins
authors.affiliation: Pediatric Allergy, Asthma and Immunology Clinic, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. nraje@cmh.edu.
authors.forename: Nikita
authors.initials: N
authors.lastname: Raje
authors.affiliation: Dermatology Clinic, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. kmcanty@cmh.edu.
authors.forename: Kristi
authors.initials: K
authors.lastname: Canty
authors.affiliation: Department of Hematology and Oncology, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. msharma@cmh.edu.
authors.forename: Mukta
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Division of Clinical Genetics, Childrens Mercy Hospital, 2420 Pershing Road, Suite 421, Kansas City, MO, 64108, USA. lgrote@cmh.edu.|Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. lgrote@cmh.edu.|University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. lgrote@cmh.edu.
authors.forename: Lauren
authors.initials: L
authors.lastname: Grote
authors.affiliation: Division of Clinical Genetics, Childrens Mercy Hospital, 2420 Pershing Road, Suite 421, Kansas City, MO, 64108, USA. hwelsh@cmh.edu.|Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. hwelsh@cmh.edu.|University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. hwelsh@cmh.edu.
authors.forename: Holly I
authors.initials: HI
authors.lastname: Welsh
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. egfarrow@cmh.edu.
authors.forename: Emily
authors.initials: E
authors.lastname: Farrow
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. gtwist@cmh.edu.
authors.forename: Greyson
authors.initials: G
authors.lastname: Twist
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. nmiller@cmh.edu.
authors.forename: Neil
authors.initials: N
authors.lastname: Miller
authors.affiliation: Department of Pathology and Laboratory Medicine, Childrens Mercy Hospitals, Kansas City, MO, 64108, USA. dzwick58@gmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Zwick
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. lazellmer@cmh.edu.
authors.forename: Lee
authors.initials: L
authors.lastname: Zellmer
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, 64108, USA. sfkingsmore@cmh.edu.|Department of Pathology and Laboratory Medicine, Childrens Mercy Hospitals, Kansas City, MO, 64108, USA. sfkingsmore@cmh.edu.|Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. sfkingsmore@cmh.edu.|University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. sfkingsmore@cmh.edu.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Kingsmore
authors.affiliation: Division of Clinical Genetics, Childrens Mercy Hospital, 2420 Pershing Road, Suite 421, Kansas City, MO, 64108, USA. nsafina@cmh.edu.|Department of Pediatrics, Children's Mercy Hospitals, Kansas City, MO, 64108, USA. nsafina@cmh.edu.|University of Missouri, Kansas City School of Medicine, Kansas City, MO, USA. nsafina@cmh.edu.
authors.forename: Nicole P
authors.initials: NP
authors.lastname: Safina
mesh_terms: D043171:Chromosomal Instability / Q000235:genetics*; D053960:DNA Breaks; D004257:DNA Polymerase II / Q000172:deficiency* / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation; D000075223:Poly-ADP-Ribose Binding Proteins; D011247:Pregnancy
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; D004257:DNA Polymerase II; C119525:POLE protein, human