title: Next generation sequencing revealed DNA ligase IV deficiency in a "developmentally normal" patient with massive brain Epstein-Barr virus-positive diffuse large B-cell lymphoma.
abstract: BACKGROUND
  Here we present an unusual case of DNA ligase IV deficiency syndrome without dysmorphic facial findings and microcephaly complicated with Epstein-Barr virus-associated large B-cell lymphoma with the right lung involvement and a massive brain tumor lesion in a two-year-old female.
  
  
  METHODS
  PID panel was used for sequencing 55 genes. Most genes have >98% exon coverage including splicing sites. LIG4 gene has 100% exon and splicing site coverage. This was used in Ion Torrent PGM system, the library kit was made by Agilent with Haloplex technology. The sequence analysis software was Alamut, direct sequencing of LIG4 gene was performed after NGS results.
  
  
  RESULTS
  We identified three heterozygous mutations in LIG4 gene c.2736+3delC and c.8 C>T (p.A3V) inherited from mother and c.26C>T (p.T9I) - from father after PID panel sequencing and some additional polymorphisms in ATM, NOD2 and NLRP3 genes.
  
  
  CONCLUSIONS
  This case broadens the clinical spectrum of DNA ligase IV deficiency.
authors.affiliation: Research department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk region, Belarus. Electronic address: sharapovasv@gmail.com.
authors.forename: Svetlana O
authors.initials: SO
authors.lastname: Sharapova
authors.affiliation: Department of Pathology and Laboratory Medicine All Children's Hospital Johns Hopkins Medicine, St. Petersburg, FL, USA.
authors.forename: Elizabeth Yenhui
authors.initials: EY
authors.lastname: Chang
authors.affiliation: Research department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk region, Belarus.
authors.forename: Irina E
authors.initials: IE
authors.lastname: Guryanova
authors.affiliation: Research department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk region, Belarus.
authors.forename: Inna V
authors.initials: IV
authors.lastname: Proleskovskaya
authors.affiliation: Research department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk region, Belarus.
authors.forename: Alina S
authors.initials: AS
authors.lastname: Fedorova
authors.affiliation: Research department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk region, Belarus.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Rutskaya
authors.affiliation: Research department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk region, Belarus.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Aleinikova
mesh_terms: D001932:Brain Neoplasms / Q000276:immunology* / Q000821:virology; D002675:Child, Preschool; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000172:deficiency* / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D005260:Female; D004854:Herpesvirus 4, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000821:virology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology* / Q000821:virology; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000276:immunology* / Q000821:virology; D017422:Sequence Analysis, DNA
chemical_list: C000607893:LIG4 protein, human; D011088:DNA Ligases; D000072481:DNA Ligase ATP
keywords: Epstein–Barr virus-positive diffuse large B-cell lymphoma; LIG4 mutation