Heterozygous germline TET2 loss-of-function variants associated with an ALPS-like phenotype

Abstract

Germline homozygous loss-of-function mutations in TET2 result in significant childhood immunodeficiency that resembles autoimmune lymphoproliferative syndrome and predisposes one to lymphoma. The implications of heterozygous variants are less well understood. We describe four patients with heterozygous germline loss-of-function TET2 mutations who presented with B-cell lymphoma on a background of chronic lymphadenopathy and autoimmune features. This expands the association of germline TET2 mutations with lymphoma and an autoimmune lymphoproliferative syndrome-like phenotype to the heterozygous state. Assessment for TET2 mutations and germline origin should be considered in the appropriate context, as recognition of these variants may have implications on patient care.