Other mutations in the TREM 2 gene have been associated with AD, and it was previously shown that persons who carry two copies of this particular mutation (referred to as Q33X) have a very rare disorder called Nasu-Hakola disease
which is characterised by the onset of dementia in midlife and polycystic bone lesions with fractures.
Nasu-Hakola disease (MIM#221770), also known as PLOSL (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy), is characterized by unique combination of young onset progressive dementia, associated with sclerosing leukoencephalopathy, and systemic bone cysts with onset in the second to fourth decade (1, 2).
In recent years, studies have demonstrated that Nasu-Hakola disease is caused by a mutation in the TROBP gene (tyro protein tyrosine kinase binding protein; in other name; DAP12 gene, DNAX-activating protein 12) or the TREM2 gene (triggering receptor expressed on myeloid cells 2) (3).
Upon consideration of all properties of the patients including molecular analysis, we diagnosed the cases as Nasu-Hakola disease.
Nasu-Hakola disease: The first case reported by Nasu and review: The 50th Anniversary of Japanese Society of Neuropathology.
Imaging findings of Nasu-Hakola disease: a case report.
Nasu-Hakola disease and primary microglial dysfunction.
X-linked inheritance strongly suggests adrenomyeloneuropathy, Fabry disease, pre-mutation X-fragile diagnosis; dominant inheritance suggests cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), collagen type IV (Col IV) mutation, Nasu-Hakola disease (NHD), adult-onset autosomal dominant leucodystrophies (ADLD) and Alexander disease diagnosis.
CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts.
Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms.
An Italian family affected by Nasu-Hakola disease with a novel genetic mutation in the TREM2 gene.