Case Report: A child with NFKB1 haploinsufficiency explaining the linkage between immunodeficiency and short stature

We report the case of a patient with common variable immunodeficiency (CVID) presenting with short stature and treated with recombinant human growth hormone (rhGH). Whole exome sequencing revealed a novel single-nucleotide duplication in the NFKB1 gene (c.904dup, p.Ser302fs), leading to a frameshift and thus causing NFKB1 haploinsufficiency. The variant was considered pathogenic and was later found in the patient's mother, also affected by CVID. This is the first reported case of a patient with CVID due to NFKB1 mutation presenting with short stature. We analyzed the interconnection between NFKB1 and GH - IGF-1 pathways and we hypothesized a common ground for both CVID and short stature in our patient.

Automated summary

We present a case of a patient with common variable immunodeficiency (CVID) who exhibited short stature and was treated with recombinant human growth hormone (rhGH). Whole exome sequencing identified a novel pathogenic single-nucleotide duplication in the NFKB1 gene, leading to NFKB1 haploinsufficiency. This is the first reported case of CVID caused by an NFKB1 mutation presenting with short stature. The study also suggests a potential shared mechanism involving NFKB1 and GH-IGF-1 pathways for both CVID and short stature in this patient.