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 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.