TCF3 haploinsufficiency defined by immune, clinical, gene-dosage, and murine studies.

ABSTRACT:

Background

TCF3 is a transcription factor contributing to early lymphocyte differentiation. Germline monoallelic dominant negative and biallelic loss-of-function (LOF) null TCF3 mutations cause a fully penetrant severe immunodeficiency. We identified 8 individuals from 7 unrelated families with monoallelic LOF TCF3 variants presenting with immunodeficiency with incomplete clinical penetrance.

Objective

We sought to define TCF3 haploinsufficiency (HI) biology and its association with immunodeficiency.

Methods

Patient clinical data and blood samples were analyzed. Flow cytometry, Western blot analysis, plasmablast differentiation, immunoglobulin secretion, and transcriptional activity studies were conducted on individuals carrying TCF3 variants. Mice with a heterozygous

SUBMITTER: Boast B 

PROVIDER: S-EPMC10527523 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature