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Autosomal Recessive Agammaglobulinemia Due to a Homozygous Mutation in PIK3R1

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Abstract

The role of class IA phosphoinositide 3 kinases (PI3Ks) in immune function and regulation continues to expand with the identification of greater numbers of genetic variants. This case report is the second reported case of a homozygous premature stop codon within the PIK3R1 gene leading to autosomal recessive agammaglobulinemia. The proband, born to consanguineous parents, presented at 10 months of age with a history of oropharyngeal petechiae and bleeding from the mouth, gums, and tear ducts. Initial investigations revealed thrombocytopenia, neutropenia and the absence of B cells. Further genetic testing via a custom next-generation sequencing panel confirmed the presence of a homozygous mutation in PIK3R1, c.901 C>T, a premature stop codon at amino acid position 301. Given their many roles in immune regulation, recessive mutations in the PlK3R1 gene should be considered in infants presenting with hypogammaglobulinemia or agammaglobulinemia, particularly in the setting of parental consanguinity.

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Acknowledgements

The authors would like to thank the family for generously providing their permission to be included in this publication, as well as all those who contributed to the care of this patient and their sibling. Special acknowledgements to Dr. Victoria Siu for her contributions and support.

Authorship Statement

Manuscript title: A novel case of autosomal recessive agammaglobulinemia due to a homozygous mutation in PIK3R1.

All persons who meet authorship criteria are listed as authors, and all authors certify that they have participated sufficiently in the work to take public responsibility for the content, including participation in the concept, design, analysis, writing, or revision of the manuscript. Furthermore, each author certifies that this material or similar material has not been and will not be submitted to or published in any other publication before its appearance in the Journal of Clinical Immunology.

Authorship Contributions

Category 1

Conception and design of study: Paoyun Tang

Acquisition of data: Paoyun Tang, Sharan Goobie, Meghan Clynick, Julia Upton

Analysis and/or interpretation of data: Paoyun Tang, Sharan Goobie, Julia Upton

Category 2

Drafting the manuscript: Paoyun Tang, Meghan Clynick

Revising the manuscript critically for important intellectual content: Julia Upton, Sharan Goobie, Michelle Barton-Forbes, Marina Salvadori, April Price

Category 3

Approval of the version of the manuscript to be published: Paoyun Tang, Sharan Goobie, Meghan Clynick, Julia Upton, Michelle Barton-Forbes, Marina Salvadori, April Price

Author information

Authors and Affiliations

  1. Department of Pediatrics, London Health Science Centre, 800 Commissioners Road East, London, ON, N6A 5W9, Canada

    Paoyun Tang, Michelle A. Barton-Forbes, Marina I. Salvadori & April K. Price

  2. Department of Pediatrics, Division of Immunology and Allergy, Hospital for Sick Children, University of Toronto, 7280-555 University Ave, Toronto, ON, M5G 1X8, Canada

    Julia E. M. Upton

  3. Department of Dermatology, Sunnybrook Health Science Centre, Unit M1 100, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    Meghan P. Clynick

  4. Maritime Medical Genetics, Department of Pediatrics, Izaak Walton Killam (IWK) Health Centre, 5850/5980 University Avenue, PO Box 9700, Halifax, NS, B3K 6R8, Canada

    Sharan L. Goobie

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  1. Paoyun Tang
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Corresponding author

Correspondence to Sharan L. Goobie.

Ethics declarations

Informed consent from the family for inclusion in this report was obtained with a translator present.

Conflict of Interest

JU is a member of the Medical Advisory Board for Immunodeficiency Canada and her institution received research support from Kedrion. The remaining authors declare that they have no conflicts of interest.

Additional information

Statement of Novelty

This case report identifies a novel recessive mutation in exon 7 of the PIK3R1 gene in a female with autosomal recessive agammaglobulinemia.

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Tang, P., Upton, J.E.M., Barton-Forbes, M.A. et al. Autosomal Recessive Agammaglobulinemia Due to a Homozygous Mutation in PIK3R1 . J Clin Immunol 38, 88–95 (2018). https://doi.org/10.1007/s10875-017-0462-y

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