title: The hyper-IgE syndrome is not caused by a microdeletion syndrome.
abstract: The hyper-immunoglobulin E syndrome (HIES) is a rare primary immunodeficiency characterized by recurrent infections, elevated serum IgE-levels, and involvement of the soft- and bony tissues. We speculated that this complex disease may be caused by a microdeletion syndrome. We therefore analyzed 30 sporadic HIES patients for the presence of chromosomal imbalances using Affymetrix 50k XbaI and 23 of the 30 patients with the higher-resolution 250k StyI SNP mapping arrays. We detected only eight different copy number alterations in six patients with the 50k approach, and seven of these presented known polymorphic regions not associated with disease. However, one patient showed a unique gain on chromosome 20p. 250k array analysis identified this gain as a rare polymorphism segregating in the patient's family, but not associated with the HIES phenotype. In addition, 265 known and novel copy number variants (CNVs) were identified with the 250k arrays, but no recurrent imbalances reminescent of a microdeletion syndrome were found. We aligned the identified CNVs with loci that have been associated with HIES or phenotypically overlapping syndromes. Doing so, a 2-Mb deletion spanning the PEPD gene on 19q13.11 was identified on one allele of one patient. Homozygous mutations in PEPD are responsible for the autosomal-recessive prolidase deficiency which resembles HIES in some aspects. Sequencing of the healthy allele, however, revealed a wild-type sequence. In summary, our results suggest that HIES is not likely to be a microdeletion syndrome.
authors.affiliation: Department of Hematology and Oncology, University Hospital Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pfeifer
authors.forename: Cristina
authors.initials: C
authors.lastname: Woellner
authors.forename: Astrid
authors.initials: A
authors.lastname: Petersen
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Pietrogrande
authors.forename: Josè Luis
authors.initials: JL
authors.lastname: Franco
authors.forename: Mehdi
authors.initials: M
authors.lastname: Yeganeh
authors.forename: Stephan
authors.initials: S
authors.lastname: Ehl
authors.forename: Nuria
authors.initials: N
authors.lastname: Matamoros
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Puck
authors.forename: Hendrik
authors.initials: H
authors.lastname: Veelken
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
mesh_terms: D002872:Chromosome Deletion; D002877:Chromosomes, Human / Q000235:genetics*; D004150:Dipeptidases / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006720:Homozygote; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007589:Job Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D008297:Male; D020125:Mutation, Missense; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D007073:Immunoglobulin E; D004150:Dipeptidases; C022449:proline dipeptidase