Immune System Diseases study with SNP/CNV Genotypes (NGS) data on dbGaP (23 participants)

phs002816 — Genetic Diseases of Immune Homeostasis and Autoimmunity Caused by GIMAP    Deficiency

We investigated 17 affected individuals in 9 kindreds with lymphopenia, splenomegaly, liver disease, thrombocytopenia, lymphadenopathy, severe recurrent lung infections, skin diseases, and lymphoma. Whole-exome sequencing of the cohort revealed mutations in <a href="https://www.ncbi.nlm.nih.gov/gene/55340">GIMAP5</a>.
We also found another patient from one kindred with a unique mutation in the gene <a href="https://www.ncbi.nlm.nih.gov/gene/474344">GIMAP6</a>, discovered by whole-exome sequencing. A comprehensive investigation of this gene mutation through in vivo and in vitro experiments revealed that GIMAP6 deficiency results in defects in autophagy in patient T cells and interruption of <a href="https://www.ncbi.nlm.nih.gov/gene/168537">GIMAP7</a> and <a href="https://www.ncbi.nlm.nih.gov/gene/11345">GABARAPL2</a> interactions. GIMAP6 deficiency leads to affected patients to present with clinical phenotypes such as recurrent infections, lymphoproliferation, autoimmunity, and inflammation.