The clinical and laboratory spectrum of dedicator of cytokinesis 8 immunodeficiency syndrome in patients with a unique mutation

Arnon Broides, Amarilla B. Mandola, Jacov Levy, Baruch Yerushalmi, Vered Pinsk, Michal Eldan, George Shubinsky, Nurit Hadad, Rachel Levy, Amit Nahum, Miriam Ben-Harosh, Atar Lev, Amos Simon, Raz Somech

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish
Pages (from-to)651-657
Number of pages7
JournalImmunologic Research
Volume65
Issue number3
DOIs
StatePublished - 1 Jun 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017, Springer Science+Business Media New York.

Funding

The authors are indebted to Mrs. I. Dulman and Mrs. T. Gershberg for excellent technical assistance. The work performed by GS was partially supported by the Israeli Ministry of Immigrant Absorption.

FundersFunder number
Ministry of Aliyah and Immigrant Absorption

    Keywords

    • Combined immunodeficiency
    • Genotype
    • IgE
    • Phenotype

    Fingerprint

    Dive into the research topics of 'The clinical and laboratory spectrum of dedicator of cytokinesis 8 immunodeficiency syndrome in patients with a unique mutation'. Together they form a unique fingerprint.

    Cite this