Update on the genetic basis and therapeutic perspectives in X-linked agammaglobulinemia
Keywords:
AGAMMABLOBULINEMIA, CROMOSOMA X, ENFERMEDADES DE INMUNODEFICIENCIA PRIMARIA, ENFERMEDADES DEL SISTEMA INMUNE.Abstract
Introduction: primary immunodeficiencies constitute a group of diseases with a genetic basis due to quantitative or functional alterations of different mechanisms involved in the immune response. According to their inheritance pattern they can be autosomal dominant and recessive or X-linked.
Objective: to describe the genetic basis and therapeutic perspectives of X-linked agammaglobulinemia. Methods: A literature review was performed by searching the Medline/PubMed, Bireme (Scielo, Lilacs) and Cochrane Medical Library databases in October and November 2023 using an advanced search formula.
Development: currently more than 350 primary immunodeficiencies have been described, of which more than 250 have been mapped with the responsible gene and it is suspected that about 3000 genes could be related to their origin. X-linked agammaglobulinemia results from loss of function variants in the Bruton's tyrosine kinase gene with gene locus on the long arm of the X chromosome in which more than 700 exonic and intronic mutations have been described.
Conclusions: the complexity of the molecular diagnosis of these disorders lies in the fact of the great genetic heterogeneity they present. Immunoglobulin replacement therapy remains the main therapeutic tool. Gene editing is a promising approach to treat X-linked agammaglobulinemia and inborn errors of immunity in general.
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