Primary immunodeficiencies (PID) are a heterogeneous group of inborn errors of immunity. The phenotypical heterogeneity of PID leads to diagnostic difficulties. Pathogenic variants in over 430 genes can cause PID. Identifying a specific genetic cause of PID facilitates definitive treatment and contributes to our understanding of the human immune system.
The aim of the study was to characterize the results of PID genetic testing since the application of next generation sequencing (NGS) technique has become the first line genetic testing in Latvia. Retrospective data from the Children’s Clinical University Hospital Clinic of Medical Genetics and Prenatal Diagnostics during time period from 2018 till 2020. A total of 22 patients (median age 8 years, ranging from 3 month to 31 years) were sent for genetic testing due to clinical suspicions of PID. Clinically this is a heterogeneous group of patients with periodic fevers, recurrent severe infections as sepsis and osteomyelitis, severe autoimmune disorders etc. Twenty one patients were sent for the analysis of a selected PID genes panel (274 genes in 2018, updated to 298 in 2019), and one patient - for open exome analysis. In 16 (72%) patients, the testing results were negative, in two (10%) patients – a variant of uncertain significance was identified, and in four (18%) patients – pathogenic or likely pathogenic variants in different genes were identified:PIK3CD:c.1573G>A,(p.Glu525Lys) causing immunodeficiency-14; CYBB:c.676C>T,(p.Arg226*) confirming X-linked chronic granulomatous disease; STAT1:c.A>C,(p.Gln271Pro) causing immunodeficiency-31 and SH2D1A:c.5A>G,(p.Asp2Gly) confirming X-linked lymphoproliferative syndrome. PID genetic testing is challenging and even after broad PID gene panel testing the genetic cause was found only in 4/22 (18%) cases. There is a need for better genetic diagnostic tools than currently available (e.g. whole genome and transcriptome sequencing, or multi-Omics approach) to uncover the genetic cause for the other PID patients.
- 3.4. Other publications in conference proceedings (including local)