Loss of Function Mutation in ELF4 Causes Autoinflammatory and Immunodeficiency Disease in Human

Overview

Journal J Clin Immunol

Publisher Springer

Specialty Allergy & Immunology

Date 2022 Mar 10

PMID 35266071

Authors

Gan Sun

Luyao Qiu

Lang Yu

Yunfei An

Yuan Ding

Lina Zhou

Junfeng Wu

Xi Yang

Zhiyong Zhang

Xuemei Tang

Huawei Xia

Lili Cao

Fuping You

Xiaodong Zhao

Hongqiang Du

Affiliations

Soon will be listed here.

Abstract

Monogenic autoinflammatory diseases (mAIDs) are a heterogeneous group of diseases affecting primarily innate immunity, with various genetic causes. Genetic diagnosis of mAIDs can assist in the patient's management and therapy. However, a large number of sporadic and familial cases remain genetically uncharacterized. Deficiency in ELF4, X-linked (DEX) is recently identified as a novel mAID. Here, we described a pediatric patient suffering from recurrent viral and bacterial respiratory infection, refractory oral ulcer, constipation, and arthritis. Whole-exome sequencing found a hemizygous variant in ELF4 (chrX:129205133 A > G, c.691 T > C, p.W231R). Using cells from patient and point mutation mice, we showed mutant cells failed to restrict viral replication effectively and produced more pro-inflammatory cytokines. RNA-seq identified several potential critical antiviral and anti-inflammation genes with decreased expression, and ChIP-qPCR assay suggested mutant ELF4 failed to bind to the promoters of these genes. Thus, we presented the second report of DEX.

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