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

Svetlana O Sharapova; Elizabeth Yenhui Chang; Irina E Guryanova; Inna V Proleskovskaya; Alina S Fedorova; Elena A Rutskaya; Olga V Aleinikova

doi:10.1016/j.clim.2016.01.002

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

Clin Immunol. 2016 Feb:163:108-10. doi: 10.1016/j.clim.2016.01.002. Epub 2016 Jan 13.

Authors

Svetlana O Sharapova¹, Elizabeth Yenhui Chang², Irina E Guryanova³, Inna V Proleskovskaya³, Alina S Fedorova³, Elena A Rutskaya³, Olga V Aleinikova³

Affiliations

¹ Research department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk region, Belarus. Electronic address: sharapovasv@gmail.com.
² Department of Pathology and Laboratory Medicine All Children's Hospital Johns Hopkins Medicine, St. Petersburg, FL, USA.
³ Research department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk region, Belarus.

PMID: 26774591
DOI: 10.1016/j.clim.2016.01.002

Abstract

Introduction: 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.

Result: 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.

Conclusion: This case broadens the clinical spectrum of DNA ligase IV deficiency.

Keywords: Epstein–Barr virus-positive diffuse large B-cell lymphoma; LIG4 mutation.

Publication types

Case Reports
Letter
Research Support, Non-U.S. Gov't

MeSH terms

Brain Neoplasms / immunology*
Brain Neoplasms / virology
Child, Preschool
DNA Ligase ATP
DNA Ligases / deficiency*
DNA Ligases / genetics
Epstein-Barr Virus Infections / immunology*
Female
Herpesvirus 4, Human
High-Throughput Nucleotide Sequencing
Humans
Immunologic Deficiency Syndromes / genetics
Immunologic Deficiency Syndromes / immunology*
Lung Neoplasms / immunology*
Lung Neoplasms / virology
Lymphoma, Large B-Cell, Diffuse / immunology*
Lymphoma, Large B-Cell, Diffuse / virology
Mutation
Neoplasms, Multiple Primary / immunology*
Neoplasms, Multiple Primary / virology
Sequence Analysis, DNA

Substances

LIG4 protein, human
DNA Ligases
DNA Ligase ATP