Clinical and immunological characterization of a child with a homozygous TBK1 kinase-domain truncation

Clinical Heterogeneity of TNFRSF13B Variants: A Monogenic Cause or a Genetic Modifier?

Patients with TNFRSF13B variants display broad phenotypic heterogeneity ranging from asymptomatic carriage to CVID and combined immunodeficiency phenotypes, suggesting that coexisting genetic variants and exposomal factors likely determine the clinical expression and disease severity.

Paediatric rheumatology Functional characterisation of a novel homozygous p.Y227C ADA2 variant in a child with deficiency of adenosine deaminase type 2

The private truncating Toll-like receptor 7 p.Glu834* variant associates with juvenile-onset systemic lupus erythematosus and pathological cytokine expression in vitro.

OBJECTIVES The X chromosome-linked Toll-like receptor (TLR)7 gene contributes to type I interferon (IFN) expression in systemic lupus erythematosus (SLE). Recently, ultra-rare variants in TLR7 have been linked with Mendelian forms of SLE. METHODS Targeted new-generation sequencing was used to identify TLR7 coding var...

A Novel Dominant-negative CARD11 Variant Causes Atopy and Immunodeficiency Syndrome

CARD11 is a multidomain scaffolding protein essential for antigen receptor-induced NF-κB signaling in lymphocytes. CARD11 is highly intolerant to mutations, and pathogenic variants have been implicated in various immune-related disorders. In this study, we describe a family with a novel CARD11 missense variant,...

Mild Phenotype in Functionally Validated STAT1 Gain-of-Function Disease Due to a Novel DNA-Binding Variant.

Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) disease is associated with chronic mucocutaneous candidiasis, infections, autoimmunity, and immune dysregulation; however, mutation-level determinants of phenotypic variability remain incompletely defined. We aimed to describe the clinica...

CARD9 Deficiency Mimicking Hyper-IgE Syndrome

Caspase recruitment domain-containing protein 9 (CARD9) deficiency is a rare primary immunodeficiency characterized by a profound susceptibility to invasive fungal infections. Given its significant phenotypic overlap with hyper-IgE syndrome (HIES)—most notably, markedly elevated serum IgE levels—misdiagnosis remains...