T-Cell Immunodeficiencies With Congenital Alterations of Thymic Development: Genes Implicated and Differential Immunological and Clinical Features

• Published in: Frontiers in immunology Vol. 11; p. 1837
• Main Authors: Giardino, Giuliana, Borzacchiello, Carla, De Luca, Martina, Romano, Roberta, Prencipe, Rosaria, Cirillo, Emilia, Pignata, Claudio
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 14.08.2020
• Subjects: CHARGE; CHD7 gene; FOXN1 gene; Humans; Immunology; Pax 1/9; PAX1 gene; Severe Combined Immunodeficiency - genetics; Severe Combined Immunodeficiency - immunology; Severe Combined Immunodeficiency - pathology; T-Lymphocytes - immunology; Thymus; Thymus Gland - abnormalities; Thymus Gland - embryology; Thymus Gland - immunology; Pax 1/9; FOXN1 gene; DiGeorge anomaly; TBX1 gene; CHARGE; CHD7 gene; PAX1 gene; Thymus
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.01837

Combined Immunodeficiencies (CID) are rare congenital disorders characterized by defective T-cell development that may be associated with B- and NK-cell deficiency. They are usually due to alterations in genes expressed in hematopoietic precursors but in few cases, they are caused by impaired thymic development. Athymia was classically associated with DiGeorge Syndrome due to gene haploinsufficiency. Other genes, implicated in thymic organogenesis include , associated with Nude SCID syndrome, , associated with Otofaciocervical Syndrome type 2, and , one of the genes implicated in CHARGE syndrome. More recently, chromosome 2p11.2 microdeletion, causing haploinsufficiency, has been identified in 5 families with impaired thymus development. In this review, we will summarize the main genetic, clinical, and immunological features related to the abovementioned gene mutations. We will also focus on different therapeutic approaches to treat SCID in these patients.