About this Research Topic
Rare diseases of the immune system present with immense clinical variability, which includes features of systemic inflammation, autoimmunity, immunodeficiency, and increased risk for neoplasia. Molecular diagnostics has become an integral part of clinical practice as it can guide physicians in establishing definitive diagnosis and in choosing appropriate treatment strategies. Next-generation sequencing (NGS)-based methods have become the new “gold-standard” approaches for molecular testing worldwide, with targeted gene panel sequencing (TGP), whole-exome sequencing (WES), and whole-genome sequencing (WGS) as the most widely used. However, their diagnostic yield for patients with inborn errors of immunity is surprisingly low. The performance of TGPs is probably not higher than 20%, except in founder populations, whereas that from WES is about 25-30%, a slight increase from the TGP. The low diagnostic yield can be attributed to technological deficiencies (poor coverage), challenges in variant interpretation, lack of population-specific databases, deficiency of relevant functional assays, inadequate search for copy number variations, structural variants or mosaicism, or wrong testing indications.
This Research Topic aims to gain information on the diagnostic yield in laboratories performing molecular testing for patients suspected to have inborn errors of immunity, including suspected monogenic autoinflammatory, early-onset autoimmune diseases, and classical primary immunodeficiencies. Based on the high variability in the genetics of different human populations around the world and the differences in each country to have access to molecular testing, we would like to publish reports from labs that perform this type of molecular testing to know the real landscape about this issue, and also to know the problems they are challenging in their daily work.
We are interested in Original Research, Brief Research Report, Case Report, Perspective, and Review/Mini Review articles that further our understanding of the following areas of monogenic immune disease and classical immunodeficiencies diagnostics:
• Cohort description
• Description of NGS-based testing technology
• Data processing and analysis
• Method’s limitations to identify structural gene variants
• Variant interpretation, including limitations to the current ACMG guidelines for GoF variants
• Functional tests and diagnostic yield
• Will WGS be the future gold-standard method in genetic labs?
This Research Topic aims to gain information on the diagnostic yield in laboratories performing molecular testing for patients suspected to have inborn errors of immunity, including suspected monogenic autoinflammatory, early-onset autoimmune diseases, and classical primary immunodeficiencies. Based on the high variability in the genetics of different human populations around the world and the differences in each country to have access to molecular testing, we would like to publish reports from labs that perform this type of molecular testing to know the real landscape about this issue, and also to know the problems they are challenging in their daily work.
We are interested in Original Research, Brief Research Report, Case Report, Perspective, and Review/Mini Review articles that further our understanding of the following areas of monogenic immune disease and classical immunodeficiencies diagnostics:
• Cohort description
• Description of NGS-based testing technology
• Data processing and analysis
• Method’s limitations to identify structural gene variants
• Variant interpretation, including limitations to the current ACMG guidelines for GoF variants
• Functional tests and diagnostic yield
• Will WGS be the future gold-standard method in genetic labs?
Keywords: Inborn errors of immunity, Monogenic autoinflammatory diseases, Early-onset autoimmune diseases, Primary immunodeficiencies, Next-generation sequencing (NGS), Molecular diagnostics
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
