NEW PATHOGENIC VARIANT ON IL-7R GENE ASSOCIATED WITH SCID

Abstract

Introduction T-B+NK+ Severe Combined Immunodeficiency (SCID) due to mutations in the genes encoding the IL-7 receptor represent about 10% of American SCID cases. We report a patient found to have a c.675C>A (p.Tyr225*) homozygous mutation in exon 5. This variant is not present in population databases, and has not been reported in the literature in individuals with IL-7 receptor disease. Case Description Our medical center received a referral for abnormal T-cell receptor excision circle (TREC) results on a newborn screen. The patient's mother had an uncomplicated pregnancy, and there was no consanguinity or family history concerning for a primary immune deficiency. Lymphocyte subsets revealed an absence of T cells, along with present, but diminished B-cells and Natural-Killer cells. The patient had an absent thymic shadow on chest X-ray. He was also found to have poor mitogenic responses. FISH for DiGeorge syndrome was negative for deletions in 22q11.2 and 22q13, and testing for ADA deficiency was negative. Genetic testing resulted in a c.675C>A (p.Tyr225*) homozygous mutation. The patient has had a confirmed infection with Rhinovirus. He is currently on bacterial and fungal prophylaxis, and receiving immune globulin while awaiting bone marrow transplantation. Discussion A homozygous mutation in IL7R, Exon 5, c.675C>A (p.Tyr225*) creates a premature translational stop signal in the IL7R gene, resulting in an absent or disrupted protein product. Loss of function variants of IL7R are known to be pathogenic. This case reinforces the need for researchers to functionally evaluate all mutations found in patients.