AUTHOR=Giardino Giuliana , Borzacchiello Carla , De Luca Martina , Romano Roberta , Prencipe Rosaria , Cirillo Emilia , Pignata Claudio 

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

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01837

DOI=10.3389/fimmu.2020.01837

ISSN=1664-3224

ABSTRACT=<p>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 <italic>TBX1</italic> gene haploinsufficiency. Other genes, implicated in thymic organogenesis include <italic>FOXN1</italic>, associated with Nude SCID syndrome, <italic>PAX1</italic>, associated with Otofaciocervical Syndrome type 2, and <italic>CHD7</italic>, one of the genes implicated in CHARGE syndrome. More recently, chromosome 2p11.2 microdeletion, causing <italic>FOXI3</italic> 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.</p>