Name: Hyper-IgE recurrent infection syndrome 3 | Acronym: HIES3
Alt. names: ZNF341 deficiency

Gene: ZNF341 | MOI: Autosomal recessive | Mechanism of action: Loss of Function

No. of cases in DB: 20 | First reported in: 2018

Last updated on: 2023-03-28 17:19:41 by Xiao P. Peng

OMIM: 618282

Orphanet: 641368

MONDO: 0032654

DOID: 0080595

ClinGen: Definitive (2024-06-04)

Beziat et al. (2018) and Frey-Jakobs et al. (2018) identified biallelic ZNF341 loss of function (LOF) variants associated with a recessively inherited hyper-IgE syndrome (HIES)-like phenotype in nineteen total patients from ten unrelated families of diverse ancestries, all of whom shared a family history of consanguinity (PMID: 29907690, 29907691). Like those with AD-HIES due to STAT3 dominant negative mutations, these patients presented with susceptibility to recurrent fungal and bacterial infections, particularly chronic mucocutaneous candidiasis (CMC) and Staphylococcal infections, severe early onset atopy including eczema, but stronger inflammatory responses. Similar extra-hematopoietic manifestations i.e. craniofacial, dental, vascular and connective tissue involvement were also seen but less frequently. Finally, there is a suggestion that both STAT3-HIES and ZNF341 deficiency may lead to increased radiosensitivity and impaired DNA repair, potentially linked to an increased malignancy susceptibility (PMID: 31980991, 35511492). Immunophenotyping showed high serum IgE and IgG levels, normal in vitro T cell proliferation in response to mitogens and antigens, and normal or subnormal antigen-specific antibody responses. Patients had variable eosinophilia, grossly normal T and B cell counts, but reduced levels of NK cells, memory B cells and Th17 CD4+ T cells.

Anti-microbial prophylaxis and early and aggressive treatment of infections may be beneficial for decreasing morbidity and mortality. Dupilumab has been shown effective for treating STAT3-HIES and can be considered for this condition (PMID: 34536614, 34417287, 35470938, 35734823, 32360519).