Molecular and immunological characterization of DNA ligase IV deficiency

Abstract DNA ligaseIV ( LIG4) deficiency is an extremely rare autosomal recessive primary immunodeficiencydisease caused by the LIG4mutation. To date, fewer than 30 cases of patients have been reported worldwide. No reversion mutations have been previously identified in LIG4. This study enrolled seven Chinese patients with LIG4deficiency who presented with combined immunodeficiency, microcephaly, and growth retardation. One patient (P1) acquired non-Hodgkin lymphoma. Four patients had impaired T cell proliferation function and skewed T cell receptor diversity. Five novel mutations in LIG4and a potential hotspot mutation (c.833G > T; p.R278L) in the Chinese population were identified. TA cloninganalysis of T cells, NK cells, granulocytes, and oral mucosacells in P6 revealed wild-type clones and clones that contained both maternally and paternally inherited mutations, indicating possible somatic reversion which need further investigation since no functional or protein assays were possible for all the patients died and no cell lines were available.