Novel Compound Heterozygous Mutations in IL-7 Receptor α Gene in a 15-Month-Old Girl Presenting With Thrombocytopenia, Normal T Cell Count and Maternal Engraftment

Abstract

Patients with severe combined immunodeficiency (SCID) exhibit T lymphopenia and profound impairments in cellular and humoral immunity. IL-7 receptor α (IL-7Rα) deficiency is a rare form of SCID that usually presents in the first months of life with severe and opportunistic infections, failure to thrive and high risk of mortality unless treated. Here, we reported an atypical and delayed onset of IL7Rα-SCID in a 15-month-old girl presenting with thrombocytopenia. Immunological investigations showed a normal lymphocyte count with isolated CD4-penia, absence of naïve T cells, marked hypergammaglobulinemia, and maternal T cell engraftment. Targeted next generation sequencing (NGS) revealed two novel compound heterozygous mutations in the IL-7Rα gene: c.160T>C (p.S54P) and c.245G>T (p.C82F). The atypical onset and the unusual immunological phenotype expressed by our patient highlights the diagnostic challenge in the field of primary immunodeficiencies (PID) and in particular in SCID patients where prompt diagnosis and therapy greatly affects survival.

Keywords: IL-7Rα gene; SCID; atypical onset; maternal engraftment; novel compound heterozygous mutations.

Figure 1

(A) Sequence alignment of the patient's BAM file on IGV (Integrative Genomics Viewer) and the two heterozygous mutation found by IL7R DNA sequencing. (B) Patient's genealogical tree.

Figure 2

Phenotypic and pSTAT5 signaling in patient's relatives and in patient derived lymphocytes. (A) IL-7Rα (CD 127) surface expression were assessed by means of multiparameter flow cytometry in T cell subset. (B) The phosphorylation status of STAT5 (Y694) was determined by means of Phosflow analysis after IL-7 treatment in T cell subsets.