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Spectrum of Phenotypes Associated with Mutations in LRBA

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Abstract

To date, several germline mutations have been identified in the LRBA gene in patients suffering from a variety of clinical symptoms. These mutations abolish the expression of the LRBA protein, leading to autoimmunity, chronic diarrhea, B-cell deficiency, hypogammaglobulinemia, functional T-cell defects and aberrant autophagy. We review the clinical and laboratory features of patients with LRBA mutations and present five novel mutations in eight patients suffering from a multitude of clinical features.

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Contribution

O.K. and H.A. performed experiments, analyzed results, made the figures, and wrote the paper; M.F. analyzed results; K.K., M.M, and J.C. performed experiments and analyzed results; H.A., Z.C., I.M., and M.E. performed clinical sampling and; A.A., N.R., R.G. and L.H. designed the research and edited the paper.

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Authors and Affiliations

  1. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden

    Omar K. Alkhairy, Hassan Abolhassani, Mingyan Fang, Kasper Krogh Andersen & Lennart Hammarström

  2. Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia

    Omar K. Alkhairy

  3. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Hassan Abolhassani, Nima Rezaei & Asghar Aghamohammadi

  4. Department of Immunology, School of Medicine, and Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

  5. BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen, China

    Mingyan Fang

  6. Pediatric Infectious Research Center, Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Zahra Chavoshzadeh

  7. Noncommunicable Pediatric Diseases Research Center, Amirkola Hospital, Babol University of Medical Sciences, Babol, Iran

    Iraj Mohammadzadeh

  8. Department of Pediatrics, Makassed General Hospital, Beirut, Lebanon

    Mariam A. El-Rajab

  9. Division of Immunology, Boston Children’s Hospital and the Department of Pediatrics, Harvard Medical School, Boston, MA, USA

    Michel Massaad, Janet Chou & Raif S. Geha

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  1. Omar K. Alkhairy
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Corresponding author

Correspondence to Lennart Hammarström.

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Financial Resources

This work was supported by the Jeffrey Modell Foundation and the Swedish Research Council.

Conflict of Interest

The authors declare no competing financial interests.

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Supplementary Table 1

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Supplementary Table 2

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Supplementary Table 3

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Supplementary Table 4

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Supplementary Table 5

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Supplementary Table 6

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Multiple Choice Questions

Multiple Choice Questions

Somatic mutations in LRBA have been linked to:

  1. 1.

    Chronic diarrhea

  2. 2.

    Immune thrombocytopenic purpura

  3. 3.

    Autoimmune hemolytic anemia

  4. 4.

    Breast cancer

  5. 5.

    Hypogammaglobulinemia

In LRBA deficiency, B-cell characteristics most commonly include:

  1. 1.

    An increased proportion of switched memory B-cells

  2. 2.

    A decreased proportion of switched memory B-cells

  3. 3.

    Normal autophagic function

  4. 4.

    Normal B-cell proliferation

  5. 5.

    Normal B-cell differentiation

Regarding mutations resulting in LRBA, which of the following statments is correct:

  1. 1.

    Only fragment deletions result in LRBA deficiency

  2. 2.

    Only nonsense mutations result in LRBA deficiency

  3. 3.

    Only mutations in exon 30 result in LRBA deficiency

  4. 4.

    Multiple mutations are necessary to result in LRBA deficiency

  5. 5.

    A single homozygous mutation may result in LRBA deficiency

LRBA is a:

  1. 1.

    Cell-surface receptor protein

  2. 2.

    Expressed in lymphoid cells only

  3. 3.

    Expressed in neural cells only

  4. 4.

    Expressed in B-cells only

  5. 5.

    Cytosolic protein

Regarding plasma cells, which of the following is correct :

  1. 1.

    Do not have autophagic activity

  2. 2.

    Have high autophagic activity

  3. 3.

    Lose their endoplasmic reticula during differentiation

  4. 4.

    Do not express autophagy-related proteins

  5. 5.

    Have a very low level of autophagy substrate SQSTM1 protein

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Alkhairy, O.K., Abolhassani, H., Rezaei, N. et al. Spectrum of Phenotypes Associated with Mutations in LRBA . J Clin Immunol 36, 33–45 (2016). https://doi.org/10.1007/s10875-015-0224-7

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  • DOI: https://doi.org/10.1007/s10875-015-0224-7

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