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.

Genetic Diseases of Immune Homeostasis and Autoimmunity Caused by GIMAP    Deficiency

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