Combined immunodeficiency caused by a loss-of-function mutation in DNA polymerase delta 1.

ABSTRACT:

Background

Mutations affecting DNA polymerases have been implicated in genomic instability and cancer development, but the mechanisms by which they can affect the immune system remain largely unexplored.

Objective

We sought to establish the role of DNA polymerase δ1 catalytic subunit (POLD1) as the cause of a primary immunodeficiency in an extended kindred.

Methods

We performed whole-exome and targeted gene sequencing, lymphocyte characterization, molecular and functional analyses of the DNA polymerase δ (Polδ) complex, and T- and B-cell antigen receptor repertoire analysis.

Results

We identified a missense mutation (c. 3178C>T; p.R1060C) in POLD1 in 3 related subjects who presented with recurrent, especially herpetic, infections and T-cell lymphopenia with imp

SUBMITTER: Cui Y 

PROVIDER: S-EPMC6961977 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature