Australian researchers used a new generation DNA sequencing technique to test a panel of 120 different immune system genes in 22 patients. They found that several patients had a genetic defect causing immunodeficiency.
- Common variable immunodeficiency (CVID) is the most common of the known primary immunodeficiency syndromes, affecting approximately one in 25,000 people.
- This disorder is characterized by decreased total serum immunoglobulin G, low immunoglobulin A and/or immunoglobulin M, and absent or impaired antibody responses to pathogenic bacteria or vaccines.
“More than 450 primary immunodeficiency disorders have been described, and this number continues to increase. Despite major advances in the molecular and genetic characterization of these disorders over the past 20 years, their rapid and accurate diagnosis remains a challenge” , said scientists from the University of Western Australia in Crawley (Australia). In a statementDr. Lloyd J. D’Orsogna, a professor in the university’s medical school, said genetic testing is expensive and mostly targets DNA sequencing of a single or very small number of genes.
130 genetic variants identified
With several Australian researchers, he decided to use a next generation DNA sequencing (NGS) technique to identify the genetic variants responsible for certain immune system disorders. In a study published in the journal The Journal of Molecular Diagnostics, the scientists recruited 22 people with common variable immunodeficiency (CVID). Participants had to present “at least one of the following criteria: an onset of the disease before the age of 18, autoimmunity, low memory B lymphocytes, family history and/or history of lymphoproliferation”, the authors said. Adult DNA samples were examined. A total of 130 genetic variants have been identified.
Probably pathogenic variants in 27% of volunteers
“Pathogenic or probably pathogenic variants were detected in 6 out of 22 patients. Mono-allelic variants of uncertain significance were also identified in four other out of 22 patients”, can we read in the works. According to the results, one patient had a new variant of the AICDA gene that had not been previously reported. Her son was diagnosed with Common Variable Immunodeficiency and also inherited the same mutation.
According to the authors, this study shows that the next-generation DNA sequencing technique is an effective tool for truly identifying disease-causing variants in patients with common variable immunodeficiency. Thus, these results will facilitate improved treatments and earlier diagnosis in family members who may have inherited the same genetic abnormality.
