Premium
P4–349: Homozygous TREM2 mutations: Another addition to the list of genetic causes of familial frontotemporal dementia
Author(s) -
Gurvit Hakan,
Bilgic Basar,
Hanagasi Hamset,
Guerreiro Rita,
Hardy John
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.08.183
Subject(s) - trem2 , frontotemporal dementia , leukoencephalopathy , dementia , medicine , pathology , semantic dementia , disease , myeloid , myeloid cells
Background: ‘Triggering receptor expressed on myeloid cells 2’ (TREM2) is a protein that is encoded by the TREM2 gene, which is located on 6p22.2 locus (OMIM 605086). Homozygous TREM2 mutations are known to cause Nasu-Hakola disease also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). PLOSL, as the name implies, is a unique disease that is characterized by multiple bone cysts and young-onset dementia. Methods: Over the recent years, we have seen 4 unrelated patients all of whom presented with a fronto-temporal dementia (FTD)-like clinical picture. All of the cases had consanguineous parents and fulfilled the revised criteria for behavioral variant FTD (bvFTD). Results: The age-of-onset varied between 20-40 years. Only one case had multiple bone cysts, which were absent in the other 3 cases. Three of them also had generalized epileptic seizures, including the single case with bone involvement. Imaging revealed almost identical findings in all: severe, prominently frontal cortical atrophy, ventricular enlargement and callosal thinning. Basal ganglia calcification was only evident in the case with bone involvement. All 3 cases without bone involvement underwent genetic analysis and were shown to harbor different homozygous mutations in TREM2 that had previously been associated with PLOSL. Conclusions: FTD-like phenotype without bone involvement had previously been shown in the 3 affected members of a Lebanese family. We propose that bone involvement is not inevitable in Nasu-Hakola disease secondary to TREM2 mutations and a bvFTD presentation in a case with consanguineous parents is a candidate for TREM2 mutation analysis. Thus, homozygous TREM2 mutations can be added to the list of genetic causes of FTD and if accepted it will be the first recessively inherited genetic cause.