CTLA4 haploinsufficiency caused by a novel heterozygous splice site mutation
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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Published In
LymphoSign Journal
Volume 9 • Number 2 • June 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
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© 2022.
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JennyGarkaby, Laura EdithAbrego Fuentes, JessicaWillett Pachul, DanieleMerico, and LindaVong. 2022. CTLA4 haploinsufficiency caused by a novel heterozygous splice site mutation. LymphoSign Journal.
9(2): 40-44. https://doi.org/10.14785/lymphosign-2022-0004
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