Clinical, Immunological and Molecular Findings of Patients with Severe Combined Immunodeficiency: Introducing of 7 Novel Mutations in 7 Genes

Abstract Purpose Severe combined immunodeficiency (SCID) is one of the severe inborn errors of the immune system associated with life-threatening infections. This disorder is characterized by diminished cellular and humoral immunity. A variable phenotype, including atypical and leaky SCID cases, as well as the heterogeneity in its genetic basis, may lead to a significant delay in diagnosis. Therefore, early diagnosis of SCID patients is crucial. Here, we describe the clinical manifestations and genetic results of four patients with SCID and four patients with atypical SCID. Methods Eight patients, who were clinically suspected to SCID, underwent immunological evaluations and genetic studies. Whole Exome Sequencing (WES) was used to identify the most relevant genetic defects which are responsible for the patients’ clinical phenotype. Further, the identified mutations were evaluated by Sanger sequencing in patients and their parents. Results All patients (4 males and 4 females) presented SCID phenotype in early infancy within 6 months of life. We found eight mutations, including two novel mutations in RAG2 (p.I273T, p.G44X), a novel 2-bp deletion in IL7R (p.F361WfsX17), a novel 2-bp deletion in LAT (p.Y207fs), a novel mutation in ADA (c.780 + 1G > A), a novel mutation in JAK3 (p.Q228Ter), a novel mutation in LIG4 (p.G428R), and also a previously reported missense mutation in RAG1 (p.A444V). All patients were homozygous, and their parents were heterozygous. Conclusion The results of our study expand the clinical and molecular spectrum associated with SCID and leaky SCID phenotypes and provide valuable information for the clinical management of our patients.