CEDS is caused by homozygous mutations in<unk> -8.<unk> -8 is a 51 kb gene with 13 exons encoding for a 496 amino acid protein that maps to 2q33.1.<unk> -8 is involved in the initiation of the cell death signal cascade. Cell death counters proliferation of lymphocytes, allowing the immune system to achieve dynamic homeostasis whereby it can defend against pathogens and avoid autoimmunity. The two reported siblings have C>T transitions, causing R248W loss-of-function mutations in the gene. The mutations lead to functional<unk>  by destabilizing the<unk> -8 protein and inactivating its enzymatic capacity. Inheritance CEDS is inherited in an autosomal recessive manner. This means affected individuals have a mutation on each of their two<unk> -8 alleles. In the case of the reported patients, the mutations were inherited from the consanguineous parents. Heterozygous carriers who have one mutated and one normal allele are healthy and lack immune-function abnormalities.
Caspase-8 deficiency
Janus kinase 3 deficiency
ZAP70 deficiency
NGLY1 deficiency
LRBA deficiency
Leukocyte adhesion molecule deficiency
CDKL5 deficiency disorder
PMM2 deficiency