Concomitant diagnosis of immune deficiency and Pseudomonas sepsis in a 19 month old with ecthyma gangrenosum by host whole-genome sequencing

Abstract

X-linked agammaglobulinemia (XLA, OMIM#300300) is a rare monogenic primary immunodeficiency caused by mutations in the Bruton tyrosine kinase (BTK) gene. XLA is characterized by insufficient immunoglobulin levels and susceptibility to life-threatening bacterial infections. We report on a patient that presented with ecthyma gangrenosum and septicemia. Rapid trio whole-genome sequencing (rWGS) revealed an apparently de novo hemizygous pathogenic variant (c.726dupT; p.Ile243TyrfsTer15) in the BTK gene. Metagenomic analysis of rWGS sequences that did not align to the human genome revealed 770 aligned to the Pseudomonas aeruginosa PAO1 genome. The patient was diagnosed with XLA and pseudomonal sepsis.

Keywords: congenital neutropenia; immune dysregulation; sepsis.

Figure 1.

Skin lesions in the affected patient showing (A) left hand, (B) left thigh, and (C) right lower leg pseudomonal ecthyma gangrenosum.

Figure 2.

Uniformly random spatial distribution of 770 reads from the proband's DNA sample (in which the y-axis represents the number of reads) aligned to the PAO1 genome (in which the x-axis is position Mb of the PAO1 genome; total size = 6.2 Mb).