We have updated our diagnostic Panel for Immune Disorders according to the latest scientific standards. With this, we will be able to clarify even more cases of rare primary immune disorders in the future through molecular genetic methods.
In this new version, we have added genes from the interim update of the Expert Committee of the International Association of Immunology Societies1 (IUIS), which publishes a regular overview of monogenic immunodeficiencies. A large part of the genes presented had already been taken into account in our gene panel, while additional genes have been added to our gene sets that cover genetic disorders such as susceptibility to infection for certain pathogen classes. A total of 19 genes have been added to our Panel for Immune Disorders, which now comprises 341 genes.
Great scientific progress has been made within the last year in the field of autoinflammatory diseases and autoimmune diseases. For example, a recent study in the New England Journal of Medicine describes a somatic change in the UBA1 gene as the cause of a disease characterized by fever, sterile inflammation and dysplastic bone marrow that starts during adulthood2. The UBA1 gene – together with five other genes – has been added to our gene set for autoinflammatory diseases as part of the update and will be considered in future cases with a corresponding indication.
Our updated analysis strategy also includes the RNA genes SNORA31 and RNU7-1, that are newly associated with susceptibility to herpes simplex encephalitis and type I interferonopathy3, 4. RNA genes are usually not examined in the context of classic exome enrichments. The Panel for Immune Disorders is based on the Exome Xtra enrichment. In addition to genes which may be associated with the patient’s disease, the analysis of ACMG genes and the pharmacogenetic profile can also be requested.
1 Tangye S. G. et al., The Ever-Increasing Array of Novel Inborn Errors of Immunity: an Interim Update by the IUIS Committee, J Clin Immunol, 2021; 41(3): 666–679, DOI: 10.1007/s10875-021-00980-1
2 Beck et al., Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease, N Engl J Med, 2020 Dec 31; 383(27):2628-2638, DOI: 10.1056/NEJMoa2026834
3 Lafaille et al., Human SNORA31 variations impair cortical neuron-intrinsic immunity to HSV-1 and underlie herpes simplex encephalitis, Nat Med, 2019, Dec;25(12):1873-1884, DOI: 10.1038/s41591-019-0672-3
4 Uggenti et al., cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing, Nat Genet, 2020,Dec;52(12):1364-1372, DOI: 10.1038/s41588-020-00737-3