Inherited mutations in the human LIG1 and LIG4 genes that result in the generation of polypeptides with partial activity have been identified as the causative factors in rare DNA ligase deficiency syndromes that share a common clinical symptom, immunodeficiency.
Here we present an unusual case of DNA ligase IVdeficiency 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.
Since LIG4 null-mutant mice are embryonic lethal and biallelic null mutations have not been described to date in LIG4-deficient patients, viability of the DNA ligase IVdeficiency syndrome appears to require at least one allele with a hypomorphic mutation.