Characterizing the molecular and clinical impact of two novel human inborn errors of immunity caused by defects in IKZF2 and ZBTB7B
department or school: Medicine, Faculty of
department or school: Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Vaseghi-Shanjani, Maryam
issued: 2025-05-31T07:00:00Z
issued: 2024
related degree: Doctor of Medicine / Doctor of Philosophy - MD/PhD
degree grantor: University of British Columbia
description: Inborn errors of immunity (IEIs) are a diverse group of genetic disorders that adversely affect the function and/or development of the immune system, resulting in increased susceptibility to infections, autoimmunity, allergy, and malignancies. Primary immune regulatory disorders and primary atopic disorders are two subcategories of IEIs. While IEIs are commonly associated with frequent, severe, and unconventional infections, primary immune regulatory disorders mainly present with immune dysregulation, and primary atopic disorders with severe, early-onset allergies. These manifestations can occur with or without the typical infectious symptoms expected with IEIs. Given the recently acknowledged diversity of symptoms associated with IEIs, there is a pressing need to sequence and investigate individuals presenting with unconventional and newly identified manifestations of IEIs. The overarching goal of this thesis was to use an established pipeline of studying single patients to discover and characterize novel monogenic causes of primary immune regulatory disorders and primary atopic disorders. The discovery of these novel classes of IEIs significantly enriches our understanding of fundamental human biology, presenting new pathways for therapeutic development and repurposing, which promise substantial enhancements in patient care. By employing a comprehensive approach that included the collection of phenotypic information from patients and the use of advanced genomic sequencing and bioinformatics analyses, we identified two novel diseases caused by germline variants in IKZF2 and ZBTB7B, which encode critical transcription factors – Helios and ThPOK – that regulate broad-ranging biological processes in the human body. The first study delineates the consequences of two dominant-negative variants in Helios, revealing an association with a complex syndrome in humans characterized by immune dysregulation and developmental anomalies, thus broadening our understanding of Helio…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/88375
note: CHARACTERIZING THE MOLECULAR AND CLINICAL IMPACT OF TWO NOVEL HUMAN INBORN ERRORS OF IMMUNITY CAUSED BY DEFECTS IN IKZF2 and ZBTB7B by Maryam Vaseghi-Shanjani B.Sc., McMaster University, 2017 M.Sc., McMaster University, 2019 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) May 2024 © Maryam Vaseghi-Shanjani, 2024 ii The following individuals certify that they have read and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation titled: “CHARACTERIZING THE MOLECULAR AND CLINICAL IMPACT OF TWO NOVEL HUMAN INBORN ERRORS OF IMMUNITY CAUSED BY DEFECTS IN IKZF2 and ZBTB7B” submitted by Maryam Vaseghi-Shanjani in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Experimental Medicine. Examining Committee: Dr. Stuart Turvey, Professor, Department of Pediatrics, UBC Supervisor Dr. Catherine Biggs, Clinical Assistant Professor, Department of Pediatrics, UBC Supervisory Committee Member Dr. Liam Brunham, Associate Professor, Department of General Internal Medicine, UBC Supervisory Committee Member Dr. Jan Friedman, Professor, Department of Medical Genetics, UBC Supervisory Committee Member Dr. Andrew Sandford, Professor, Respiratory Medicine Division, UBC Supervisory Committee Member Dr. Manish Sadarangani, Associate Professor, Department of Pediatrics, UBC University Examiner Dr. Marc Horwitz, Professor, Department of Microbiology and Immunology, UBC University Examiner Dr. Aleixo Muise, Professor, Department of Pediatrics, University of Toronto External Examiner iii Abstract Inborn errors of immunity (IEIs) are a diverse group of geneYc disorders that adversely affect the funcYon and/or development of the immune system, resulYng in increased suscepYbility to infecYons, autoimmunity, allergy, and malignancies. Primary immune regulator…
has type: Thesis/Dissertation
date issued: 2024-11
is shown at: 10.14288/1.0443774
language: eng
degree discipline: Experimental Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Turvey, Stuart E.
type: Text
identifier URI: http://hdl.handle.net/2429/88375