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Variable Clinical expressivity of STAT3 Mutation in Hyperimmunoglobulin E Syndrome: Genetic and Clinical Studies of Six Patients

Journal of Clinical Immunology volume 34, pages 163–170 (2014)Cite this article

Abstract

Background and purpose

Autosomal dominant Hyper IgE syndrome (AD-HIES) is a rare and complex primary immunodeficiency that affects multiple systems. Mutations in signal transducer and activator of transcription 3 (STAT3) gene cause AD-HIES. These mutations have a dominant-negative effect and the presence of such mutations is associated with a clinical phenotype. We aim to describe genetic and clinical characteristics of patients with AD-HIES in our clinic and to highlight the variability of clinical patterns in the same family.

Methods

We describe six patients, four individuals of the same family and two unrelated patients. All patients were given a clinical score based on disease phenotype according to the National Institute of Health (NIH) score. Mutation analysis of STAT3 was done by PCR amplification of all coding exons followed by bidirectional sequencing using the BigDye kit v1.1 and an ABI3700 genetic analyzer (Applied Biosystems).

Results

All six patients had DNA binding region point mutations: a proband and his three children with p.Phe384Leu mutation, a patient with p.Arg382Trp substitution and a patient with p.Arg382Gln mutation. All of these mutations were previously reported. Patients differed in infectious, immunologic and somatic features. We observed an extreme variability in disease phenotype within the reported family with one genetically affected patient displaying an ‘unaffected’ phenotype.

Conclusions

Although the genetic cause of AD-HIES is known, more studies are required to better understand the possible additional factors that may affect disease expressivity within families and the clinical diversity of the disease.

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Conflict of Interest

The Authors declare they have no conflict of interest.

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Affiliations

  1. Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel

    Ofir Wolach

  2. Emma Children’s Hospital, Academic Medical Center (AMC), Amsterdam, The Netherlands

    Taco Kuijpers

  3. Pediatric Intensive Care and Pediatric Pulmonology, Meir Medical Center, Kfar-Sava, Israel

    Josef Ben-Ari

  4. Laboratory for Leukocyte Function and Pediatric Immunology Clinic, Meir General Hospital, Kfar-Sava, Israel

    Ronit Gavrieli & Baruch Wolach

  5. Department of Pediatrics B and Kipper Institute of Allergy and Immunology, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel

    Neta Feinstein-Goren & Ben Zion Garty

  6. Felsenstein Medical Research Center, Tel Aviv University, Tel Aviv, Israel

    Neta Feinstein-Goren & Marielle Alders

  7. Department of Clinical Genetics, Academic Medical Center (AMC), Amsterdam, The Netherlands

    Marielle Alders

  8. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Ofir Wolach, Josef Ben-Ari, Ronit Gavrieli, Neta Feinstein-Goren, Ben Zion Garty & Baruch Wolach

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  1. Ofir Wolach
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  2. Taco Kuijpers
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  3. Josef Ben-Ari
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  4. Ronit Gavrieli
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  5. Neta Feinstein-Goren
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  6. Marielle Alders
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  7. Ben Zion Garty
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  8. Baruch Wolach
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Correspondence to Ofir Wolach.

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Wolach, O., Kuijpers, T., Ben-Ari, J. et al. Variable Clinical expressivity of STAT3 Mutation in Hyperimmunoglobulin E Syndrome: Genetic and Clinical Studies of Six Patients. J Clin Immunol 34, 163–170 (2014). https://doi.org/10.1007/s10875-014-9988-4

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  • DOI: https://doi.org/10.1007/s10875-014-9988-4

Keywords

  • Autosomal dominant Hyperimmunoglobulin E Syndrome
  • STAT3 mutations
  • Clinical expressivity