An Italian family affected by Nasu-Hakola disease with a novel genetic mutation in the trem 2 gene

Polycystic lipomembranous osteodysplasia with sclerosing leucoencephalopathy (PLOSL; MIM 221770), also known as Nasu-Hakola disease, is a recessively inherited disorder characterised by systemic bone cysts and progressive presenile dementia associated with sclerosing leucoencephalopathy. Some patients, however, do not have clinically manifest osseous problems despite the radiological demonstration of cystic bone lesions. The disease leads to death before the age of 50.1 The disease is characterised by genetic heterogeneity: mutations in two genes (TYROBP and TREM2) encoding different subunits of a membrane receptor complex in natural killer and myeloid cells have been associated with the disease.We report here the clinical and genetic analysis of an Italian family in which two siblings are affected by PLOSL. In the two affected sisters, sequencing analysis identified a homozygous C to T mutation at position 191 (191 C/T) in exon 2 of the TREM2 gene. The mutation changes glutamine 33 to a stop codon (Q33X). Our study shows that in Italy PLOSL is explained by two different mutations in TREM2 gene. Its prevalence is undetermined because the disease is likely to go unrecognised.