Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency.

ABSTRACT:

Background

Biallelic mutations in LIG4 encoding DNA-ligase 4 cause a rare immunodeficiency syndrome manifesting as infant-onset life-threatening and/or opportunistic infections, skeletal malformations, radiosensitivity and neoplasia. LIG4 is pivotal during DNA repair and during V(D)J recombination as it performs the final DNA-break sealing step.

Objectives

This study explored whether monoallelic LIG4 missense mutations may underlie immunodeficiency and autoimmunity with autosomal dominant inheritance.

Methods

Extensive flow-cytometric immune-phenotyping was performed. Rare variants of immune system genes were analyzed by whole exome sequencing. DNA repair functionality and T-cell-intrinsic DNA damage tolerance was tested with an ensemble of in vitro and in silico tool

SUBMITTER: Jauch AJ 

PROVIDER: S-EPMC10529397 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature