RESUMEN
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.
Asunto(s)
Centrómero/genética , Inestabilidad Cromosómica/genética , Cara/anomalías , Síndromes de Inmunodeficiencia/diagnóstico , Proteínas Represoras/genética , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/genética , Niño , Cromosomas Humanos/genética , Metilación de ADN , Análisis Mutacional de ADN , Progresión de la Enfermedad , Femenino , Humanos , Síndromes de Inmunodeficiencia/genética , Mutación , Fenotipo , Enfermedades de Inmunodeficiencia PrimariaRESUMEN
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.