Human JNK1 haploinsufficiency: a novel genetic etiology of chronic mucocutaneous candidiasis and connective tissue disorder

Genetic etiologies of chronic mucocutaneous candidiasis (CMC) disrupt human IL-17A/F-dependent immunity at mucosal surfaces, whereas those of connective tissue disorders (CTD) often impair the TGF-ß-dependent homeostasis of connective tissues. The signaling pathways involved are incompletely understood. We studied three patients from a three-generation family with an autosomal dominant combination of CMC and CTD. The patients carry a heterozygous loss-of-function mutation in MAPK8, the gene encoding JNK1, which impairs the cellular response to IL-17A/F and TGF-ß in their fibroblasts.