Disruption of the moonlighting function of CTF18 in a patient with T-lymphopenia.

ABSTRACT:

Introduction

Newborn screening for immunodeficiency has led to the identification of numerous cases for which the causal etiology is unknown.

Methods

Here we report the diagnosis of T lymphopenia of unknown etiology in a male proband. Whole exome sequencing (WES) was employed to nominate candidate variants, which were then analyzed functionally in zebrafish and in mice bearing orthologous mutations.

Results

WES revealed missense mutations in CHTF18 that were inherited in an autosomal recessive manner. CTF18, encoded by the CHTF18 gene, is a component of a secondary clamp loader, which is primarily thought to function by promoting DNA replication. We determined that the patient's variants in CHTF18 (CTF18 R751W and E851Q) were damaging to function

SUBMITTER: Sertori R 

PROVIDER: S-EPMC11868726 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature