Hyper IgE Syndrome in an Isolated Population in Israel.

Ronit Confino-Cohen,Ben-Zion Garty,Irina Lagovsky,Atalia Shtorch-Asor,Idit Lachover-Roth,Eyal Reinstein

doi:10.3389/fimmu.2022.829239

Abstract

IntroductionHyper IgE syndromes (HIES) are a group of rare primary immunodeficiency characterized by high levels of serum IgE, cold abscesses, pulmonary infections, and eczema. ZNF341 deficiency was described in 2018 in 11 patients clinically diagnosed previously with HIES. Eight of those patients, all offspring of consanguineous couples, are from three families who live in a Muslim village in Israel which has approximately 15,000 residents.ObjectiveOur study aimed to evaluate the prevalence of ZNF341 mutation in the population of the village.MethodsThree hundred DNA samples of females were included in the study. The samples belong to females that were referred to the Meir Medical Center for prenatal genetic testing before pregnancy, during 2017-2019: 200 samples were from the village, and 100 samples of Muslim females were from other villages.All samples were tested by Sanger sequencing for the ZNF341 mutation (c.904C>T, NM_001282933.1).ResultsHeterozygous nonsense mutation in ZNF341 was found in ten samples (5%) of the study group compared to zero in the control group (p<0.01).ConclusionThe carrier frequency of the mutation in ZNF341 in the studied village population is 1:20. This high frequency is probably due to founder mutation and consanguineous marriages.

Highlights

Hyper IgE syndromes (HIES) are a group of rare primary immunodeficiency characterized by high levels of serum IgE, cold abscesses, pulmonary infections, and eczema
signal transducer and activator of transcription 3 (STAT3) is essential for the regulation of T helper 17 (TH17) cells which are the primary source for interleukin (IL) 17, a pro-inflammatory cytokine involved in the protection against Staphylococcus aureus and Candida infections [3]
Our study aimed to evaluate the prevalence of Zinc finger 341 (ZNF341) pathogenic variant in this relatively isolated population and to compare it to the general Muslim population in Israel

Summary

Introduction

Hyper IgE syndromes (HIES) are a group of rare primary immunodeficiency characterized by high levels of serum IgE, cold abscesses, pulmonary infections, and eczema. HIES includes different disorders that are gathered together due to two common features: high levels of IgE [1], and an abnormal expression of signal transducer and activator of Abbreviations: AD, autosomal dominant; HIES, Hyper IgE syndromes; IL, Interleukin; IL6R, Interleukin 6 receptor; PID, primary immunodeficiency; STAT3, signal transducer and activator of transcription 3; TH17, T helper 17; ZNF341, zinc finger 341. Other variants that cause autosomal recessive (AR) HIES were discovered in different genes [2, 7] These pathogenic variants differ in the clinical manifestation [7] probably due to different levels of influence on STAT3 expression and activation. Other syndromes are part of the HIES, include Comel- Netherton syndrome, ERBB2interacting protein (ERBIN) deficiency, IL 6 receptor (IL6R) deficiency, IL6ST deficiency, and Loes- Dietz syndrome [11]

Methods

Results

Conclusion