Autoimmunity study with SNP/CNV Genotypes (NGS) data on dbGaP (43 participants)

phs003453 — Investigating Genetics in Suspected Congenital Syndromes

We employed forward and reverse genetics to identify individuals with heterozygous <a href="https://www.ncbi.nlm.nih.gov/gene/3716">JAK1 </a>variants associated with autoimmune and inflammatory diseases. We first recruited six unrelated probands and seven affected family members presenting with a range of autoimmune and inflammatory conditions. Whole exome sequencing revealed 4 different variants spanning all domains of the JAK1 protein: FERM domain (chr1: 64873438-G>A; c.415C>T; p.E139K), SH2 domain (chr1: 64855641-G>A; c.1516C>T; p.R506C), pseudokinase domain (chr1: 64845529-C>T; c.2099G>A; p.S700N, and kinase domain (chr1: 64838479-C>T; c.2953G>A; p.V985I). We then performed a systematic review of electronic health records of the <a href="https://icahn.mssm.edu/research/ipm/programs/biome-biobank">BioME BioBank</a> database and identified 43 additional individuals with at least one of these JAK1 variants. Comparing variant-positive and variant-negative individuals, our study revealed increased occurrences of autoimmunity, atopy, colitis, and dermatitis in patients harboring these JAK1 gain-of-function variants. We have deposited in dbGaP the whole exome sequencing files of the 43 patients identified in the BioME biobank, as well as their phenotype information.