Living with Primary Immunodeficiencies: From the Perspective of a Geneticist

Abstract

Primary immunodeficiencies represent a heterogeneous group of inherited disorders caused by defects in genes essential for immune system development and function, resulting in increased susceptibility to infections, autoimmunity, and malignancy. With over 500 identified diseases and a growing number of causative genes, understanding the genetic basis has become central to accurate diagnosis, prognosis, and family counseling. The perspective of a geneticist in helping patients live with primary immunodeficiencies would firstly involve providing patients and families with a basic understanding of what DNA, genes, mutations, and chromosomes are, as well as how genetic information is inherited (covering autosomal dominant, autosomal recessive, and X-linked recessive inheritance patterns), in order to prepare them for informed dialogue with healthcare providers. A further important role of a geneticist would be in helping patients and families understand which genetic test was performed and what it involves. Genetic diagnostics for rare diseases performed at Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade, offers several approaches, which include targeted analysis of previously detected variants via direct DNA sequencing; clinical exome sequencing, which analyzes genes with established disease associations; and whole exome sequencing, which analyzes the protein-coding regions of all genes and therefore represents the most comprehensive approach to identifying genetic causes. Explaining the diagnostic yield, limitations, and clinical implications of these tests, including the possibility of incidental findings, is an essential part of the geneticist’s role, as is ensuring that patients receive appropriate genetic counseling throughout the process. By bridging molecular genetics with everyday clinical experience, this perspective aims to support patients living with primary immunodeficiencies in better understanding their condition, anticipating implications for family planning, and engaging more confidently in shared decision-making regarding genetic testing and management.