ABSTRACT
The autosomal recessive immunodeficiency-centromeric instability-facial anomalies syndrome (ICF) is characterized by immunodeficiency, developmental delay, and facial anomalies. ICF2, caused by biallelic ZBTB24 gene mutations, is acknowledged primarily as an isolated B-cell defect. Here, we extend the phenotype spectrum by describing, in particular, for the first time the development of a combined immune defect throughout the disease course as well as putative autoimmune phenomena such as granulomatous hepatitis and nephritis. We also demonstrate impaired cell-proliferation and increased cell death of immune and non-immune cells as well as data suggesting a chromosome separation defect in addition to the known chromosome condensation defect.
Subject(s)
Centromere/genetics , Chromosomal Instability/genetics , Face/abnormalities , Immunologic Deficiency Syndromes/diagnosis , Repressor Proteins/genetics , Autoimmune Diseases/diagnosis , Autoimmune Diseases/genetics , Child , Chromosomes, Human/genetics , DNA Methylation , DNA Mutational Analysis , Disease Progression , Female , Humans , Immunologic Deficiency Syndromes/genetics , Mutation , Phenotype , Primary Immunodeficiency DiseasesABSTRACT
A 9-month-old infant presented with fatal pneumococcal sepsis and attenuated inflammation indices. Even in septic conditions, flow cytometry-based CD62L shedding test on granulocytes proved to be a fast and reliable diagnostic tool for the detection of a defect in the innate immunity. Confirmatory immunologic and genetic assays identified an autosomal-recessive interleukin-1 receptor-associated kinase-4 deficiency due to compound heterozygous mutations.
