Loss-of-function mutations in TREM2 cause Nasu-Hakola disease (NHD), a rare genetic disease characterized by early-onset dementia with leukoencephalopathy and bone cysts.
Plasma membrane receptors play primary roles as activators of microglia and in this review, we focus on a receptor complex involving triggering receptor expressed on myeloid cells 2 (TREM2) and DNAX-activating protein of 12 kDa (DAP12), both of which are causative genes for Nasu-Hakola disease, a dementia with bone cysts.
The significantly-reduced expression of TREM2 in our patients and the expression profiles of the six studied genes confirm a role for TREM2 in this distinct phenotype of EOD without bone cysts.
Surprisingly, TREM-2-deficiency in mouse led to accelerated osteoclastogenesis in vitro without osteopetrosis or bone cysts in vivo, revealing an unexpected inhibitory function of mouse TREM-2.
Recently, it has been shown that genetic defects of human DAP12/KARAP and TREM-2 result in a rare syndrome characterized by bone cysts and presenile dementia called Nasu-Hakola disease.