Journal Article

Clinical, Immunological, and Molecular Heterogeneity of 173 Patients With the Phenotype of Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked (IPEX) Syndrome

Allenspach, Eric J., Ochs, Hans D., Ciullini Mannurita, Sara, DeBoer, Stacey, Segundo, Gesmar R. S., Vignoli, Marina, Anover-Sombke, Stephanie, Favre, Claudio, Torgerson, Troy R., Hagin, David, Gambineri, Eleonora

2018

Overview

Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) Syndrome is a rare recessive disorder caused by mutations in the gene. In addition, there has been an increasing number of patients with wild-type gene and, in some cases, mutations in other immune regulatory genes. To molecularly asses a cohort of 173 patients with the IPEX phenotype and to delineate the relationship between the clinical/immunologic phenotypes and the genotypes. We reviewed the clinical presentation and laboratory characteristics of each patient and compared clinical and laboratory data of mutation-positive (IPEX patients) with those from mutation-negative patients (IPEX-like). A total of 173 affected patients underwent direct sequence analysis of the gene while 85 IPEX-like patients with normal FOXP3 were investigated by a multiplex panel of \"Primary Immune Deficiency (PID-related) genes.\" Forty-four distinct variants were identified in 88 IPEX patients, 9 of which were not previously reported. Among the 85 IPEX-like patients, 19 different disease-associated variants affecting 9 distinct genes were identified. We provide a comprehensive analysis of the clinical features and molecular bases of IPEX and IPEX-like patients. Although we were not able to identify major distinctive clinical features to differentiate IPEX from IPEX-like syndromes, we propose a simple flow-chart to effectively evaluate such patients and to focus on the most likely molecular diagnosis. Given the large number of potential candidate genes and overlapping phenotypes, selecting a panel of PID-related genes will facilitate a molecular diagnosis.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Adolescent / Adult / Amino Acid Sequence / Amino Acid Substitution / Anemia / Biomarkers / Child / Child, Preschool / Cytokines / Diagnosis / DNA Mutational Analysis / enteropathy / Female / Flow Cytometry / Forkhead Transcription Factors - genetics / FOXP3 / Foxp3 protein / Genes / Genes, X-Linked / Genetic Association Studies / Genetic Heterogeneity / Genetic Predisposition to Disease / Genotype / Genotype & phenotype / Genotypes / Hereditary diseases / High-Throughput Nucleotide Sequencing / Humans / immune dysregulation / Immunoglobulin E - immunology / Immunology / Intestinal Diseases - diagnosis / Intestinal Diseases - genetics / IPEX-like / Kaplan-Meier Estimate / Kinases / Lymphocytes / Male / Mutation / Patients / Phenotype / Phenotypes / Polyendocrinopathies, Autoimmune - diagnosis / Polyendocrinopathies, Autoimmune - etiology / Polyendocrinopathies, Autoimmune - mortality / Polyendocrinopathies, Autoimmune - therapy / polyendocrinopathy / Sequence analysis / Skin diseases / Syndrome / T-Lymphocytes, Regulatory - immunology / T-Lymphocytes, Regulatory - metabolism / X-linked (IPEX) / Young Adult