Case Report: A case series of using whole exome sequencing to detect novel variants in Vietnamese patients with inborn errors of immunity

Inborn errors of immunity (IEIs) are rare diseases that affect the immune system. Variants in over 500 genes have been identified as causative of 555 IEIs, with clinical phenotypes that can be heterogeneous within the same gene or even within the same variant. Therefore, these challenges make it difficult to determine the cause of IEI in individuals with immune disorders and to link clinical phenotypes to the precise genetic damage. An incorrect diagnosis can miss approximately 25% of IEI patients with overlapping initial manifestations. Accurate diagnosis and timely treatment are essential to improving quality of life and prolonging the lives of patients, as these patients often suffer from severe, life-threatening infections if left untreated.

In this study, whole exome sequencing (WES) was used to identify potentially pathogenic variants in six Vietnamese IEI patients. Variants in genes associated with IEIs were screened from WES data using criteria for known and/or novel pathogenic variants, and variants with minor allele frequency (MAF) < 0.001. The pathogenicity of the novel variant was assessed using The American College of Medical Genetics and Genomics (ACMG) criteria and in silico predictive software.

Six variants were identified as causative in six study patients, including c.116-2A>G (in the IL2RG gene); c.215delA, p.Asn72Ilefs*49 and c.83G>A, p.Arg28His (in the BTK gene); c.1110-3C>A (in the STAT3 gene); c.1114G>A, p.Glu372Lys (in the STAT6 gene); and c.526C>T, p.Arg176* (in the NHEJ1 gene). Of these, the variant c.1110-3C>A in the STAT3 gene was newly identified in an IEI patient.

Although this study has limitations in analyzing the WES of six patients with different types of IEI, the results will contribute to a better understanding of the genetic causes of IEIs. Furthermore, the study emphasizes the importance of accurate diagnosis, which helped improve treatment outcomes and enhance the quality of care for individuals with IEIs.