Immunologic Deficiency Syndromes study with CNV Genotypes data on dbGaP (8 participants)

phs002478 — iRHOM2 Deficiency Causes Environmentally Directed Immunodysregulatory    Disease

We have conducted a study of two kindreds each with a unique mutation in the gene <a href="https://www.ncbi.nlm.nih.gov/gene/79651">RHBDF2</a> that encodes the protein iRHOM2. Whole exome (kindred 1) and whole genome sequencing (kindred 2) have uncovered the first human loss-of-function mutations of RHBDF2 in 4 individuals. The affected patients are all children, 8 years old or younger, and were brought to our attention initially due to their suffering recurrent infections. Sequencing of their family members revealed parents with heterozygous RHBDF2 mutations, and heterozygous and wild type siblings – all of which were unaffected by this disease. A comprehensive investigation of this gene mutation through in vivo and in vitro experiments revealed that a loss of the protein iRHOM2 impairs the activity of the protease ADAM17 and subsequently compromises immune responses. This condition leads to the afflicted patients becoming vulnerable to different infections based on their unique environment and presenting with diverse clinical phenotypes.