title: The clinical and laboratory spectrum of dedicator of cytokinesis 8 immunodeficiency syndrome in patients with a unique mutation.
abstract: Mutations in the dedicator of cytokinesis 8 (DOCK8) gene cause a combined immunodeficiency usually diagnosed as autosomal recessive hyper IgE syndrome. We sought to reveal the varying manifestations in patients with a unique mutation in DOCK8 gene by a retrospective medical record review. Ten patients from five consanguineous families and three tribes were included. Seven patients were homozygous for the c.C5134A, p.S1711X mutation, and the remaining three patients were their siblings manifesting hyper IgE syndrome features without a genetic diagnosis. Prior to the genetic diagnosis, the clinical diagnosis was "hyper IgE syndrome" in six patients and "anti-pneumococcal antibody deficiency," "recurrent pneumonia with bronchiectasis," and "asthma with hypereosinophilic syndrome" each diagnosed once. One additional patient was diagnosed due to family history. The age of presentation varied from 1 to 16 months. Eczema was diagnosed in all patients, food allergies in three, and severe herpes keratitis or malignancy or autoimmunity in two patients. Elevated IgE was recorded in nine patients; however, in six patients, the initial serum IgE concentration was equal to or less than three times the normal concentration for age, and in these patients, the median age at IgE evaluation was 7.5 months compared with 21.5 months in patients with an initial IgE concentration above three times the normal concentration for age (P = 0.067). The spectrum of disease manifestations in patients with a unique mutation in DOCK8 is variable. The genotype-phenotype correlations may be modified by genetic and/or epigenetic modifiers beyond the monogenic effect. Younger patients tend to have lower IgE concentrations at the initial measurement of IgE.
authors.affiliation: Pediatric Immunology Clinic, Soroka University Medical Center, Faculty of Health Science, Ben-Gurion University of the Negev. POB151, Beer Sheva, 84101, Israel. broides@bgu.ac.il.|Soroka University Medical Center, Beer Sheva, Israel. broides@bgu.ac.il.|Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. broides@bgu.ac.il.
authors.forename: Arnon
authors.initials: A
authors.lastname: Broides
authors.affiliation: Pediatric Immunology Clinic, Soroka University Medical Center, Faculty of Health Science, Ben-Gurion University of the Negev. POB151, Beer Sheva, 84101, Israel.|Soroka University Medical Center, Beer Sheva, Israel.|Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Amarilla B
authors.initials: AB
authors.lastname: Mandola
authors.affiliation: Pediatric Immunology Clinic, Soroka University Medical Center, Faculty of Health Science, Ben-Gurion University of the Negev. POB151, Beer Sheva, 84101, Israel.|Soroka University Medical Center, Beer Sheva, Israel.|Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Jacov
authors.initials: J
authors.lastname: Levy
authors.affiliation: Soroka University Medical Center, Beer Sheva, Israel.|Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.|Pediatric Ambulatory Care Unit, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Baruch
authors.initials: B
authors.lastname: Yerushalmi
authors.affiliation: Soroka University Medical Center, Beer Sheva, Israel.|Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.|Pediatric Ambulatory Care Unit, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Vered
authors.initials: V
authors.lastname: Pinsk
authors.affiliation: Tel-Sheva Clinic, Clalit Health Services, Tel-Sheva, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Eldan
authors.affiliation: Soroka University Medical Center, Beer Sheva, Israel.|Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.|Flow Cytometry Unit, Hematology Laboratory, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: George
authors.initials: G
authors.lastname: Shubinsky
authors.affiliation: Soroka University Medical Center, Beer Sheva, Israel.|Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.|Immunology and Infectious Disease Laboratory, Department of Clinical Biochemistry, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Nurit
authors.initials: N
authors.lastname: Hadad
authors.affiliation: Soroka University Medical Center, Beer Sheva, Israel.|Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.|Immunology and Infectious Disease Laboratory, Department of Clinical Biochemistry, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Levy
authors.affiliation: Pediatric Immunology Clinic, Soroka University Medical Center, Faculty of Health Science, Ben-Gurion University of the Negev. POB151, Beer Sheva, 84101, Israel.|Soroka University Medical Center, Beer Sheva, Israel.|Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.|Pediatric Department A, Soroka University Medical Center, Beer Sheva, Israel.
authors.forename: Amit
authors.initials: A
authors.lastname: Nahum
authors.affiliation: Soroka University Medical Center, Beer Sheva, Israel.|Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.|Pediatric Hemato-Oncology Department, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Miriam
authors.initials: M
authors.lastname: Ben-Harosh
authors.affiliation: Pediatric Immunology, Safra Children's Hospital, Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel.
authors.forename: Atar
authors.initials: A
authors.lastname: Lev
authors.affiliation: Pediatric Immunology, Safra Children's Hospital, Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel.
authors.forename: Amos
authors.initials: A
authors.lastname: Simon
authors.affiliation: Pediatric Immunology, Safra Children's Hospital, Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Raz
authors.initials: R
authors.lastname: Somech
mesh_terms: D000293:Adolescent; D000367:Age Factors; D018912:Arabs; D001249:Asthma / Q000276:immunology*; D001987:Bronchiectasis / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004485:Eczema / Q000276:immunology*; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007223:Infant; D007589:Job Syndrome / Q000235:genetics / Q000276:immunology*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D012008:Recurrence; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors; D007073:Immunoglobulin E
keywords: Combined immunodeficiency; Genotype; IgE; Phenotype