Vignette #4: Two Patients with Severe Combined Immunodeficiency
(SCID)
A now 2-year-old Venezuelan male was found to have an abnormal newborn
screen showing low T-cell receptor excision circles (TRECs), with family
history significant for 2 siblings deceased as infants secondary to
presumed sepsis. Workup revealed a novel mutation in the interleukin-2
receptor gamma (IL2RG) gene, causing a loss-of-function (LOF) mutation.
LOF variants in IL2RG carry known pathogenicity, therefore this novel
variant was classified as pathogenic and the patient was diagnosed with
X-linked SCID. Testing of the patient’s father and brother were
negative, while his sister was a heterozygous carrier of the pathogenic
variant. We observed a second similar case of a 4-year-old male from the
Dominican Republic found to have a homozygous pathogenic variant in the
interleuken-7 receptor (IL7R) gene, similarly causing a novel LOF
mutation predicted to be pathogenic.