CTLA4 haploinsufficiency caused by a novel heterozygous splice site mutation

Publication: LymphoSign Journal
19 May 2022

Abstract

Background: Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) haploinsufficiency is characterized by a variety of phenotypes, ranging from autoimmune disorders, enteropathy, fatal combined immunodeficiency, as well as lymphoproliferation and malignancy.
Aim: To broaden the genotypic spectrum and clinical presentations of patients with CTLA4 variants.
Methods: We evaluated a female patient with autoimmunity and lymphopenia. Immune workup and whole exome sequencing (WES) were performed.
Results: The proband presented at 11 years of age with hypothyroidism and later developed Evans syndrome, alopecia, eczema, and lymphocytic interstitial pneumonia. Immune evaluation revealed T, B, and NK lymphopenia with normal humoral immunity. Following a negative genetic panel for autoimmune lymphoproliferative syndrome (ALPS), WES analysis identified a novel heterozygous intronic variant predicted in-silico to cause skipping of exon 2 of the CTLA4 gene.
Conclusion: A novel heterozygous mutation in CTLA4 caused variable presentations of immune dysregulation, one of the hallmarks of CTLA4 haploinsufficiency.
Statement of Novelty: We herein report a novel mutation in CTLA4 resulting in various features of autoimmunity.

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Information & Authors

Information

Published In

cover image LymphoSign Journal
LymphoSign Journal
Volume 9Number 2June 2022
Pages: 40 - 44

History

Received: 3 May 2022
Accepted: 15 May 2022
Accepted manuscript online: 19 May 2022
Version of record online: 19 May 2022

Authors

Affiliations

Jenny Garkaby [email protected]
Division of Clinical Immunology and Allergy, Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON
Laura Edith Abrego Fuentes
Division of Clinical Immunology and Allergy, Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON
Jessica Willett Pachul
Division of Clinical Immunology and Allergy, Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON
Daniele Merico
The Centre for Applied Genomics (TCAG), Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON
Vevo Therapeutics, San Francisco, CA
Linda Vong
Division of Clinical Immunology and Allergy, Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON

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