%0 Journal Article
%T Homozygous TREM2 c.549del; p.(Leu184Serfs*5) variant causing Nasu-Hakola disease in three siblings in a consanguineous Iraqi family: Case report and review of literature.
%A Gilani N
%A Bitarafan F
%A Ozaslan M
%A Åsheim S
%A Heidari M
%A Garshasbi M
%J Mol Genet Genomic Med
%V 12
%N 6
%D 2024 Jun
%M 38888203
%F 2.473
%R 10.1002/mgg3.2476
%X <B>BACKGROUND: </B>The Triggering Receptor Expressed on Myeloid Cells 2 protein (TREM2) plays a crucial role in various biological processes, including osteoclast differentiation, and disease-associated microglia (DAM) activation to regulate neuroinflammation, and phagocytosis in the brain. Genetic variations in TREM2 are implicated in neurodegenerative disorders, such as Nasu-hakola disease (NHD), characterized by bone lesions, neuropsychiatric disorders, and early-onset dementia.<BR><B>METHODS: </B>We studied 3 siblings with suspected NHD. Whole-exome sequencing was conducted on the proband to identify the possible genetic cause(s) and by Sanger sequencing to validate the identified variants in the two other affected siblings, a healthy sister, and the parents.<BR><B>RESULTS: </B>We identified a novel homozygous deletion (c.549del; p.(Leu184Serfs*5)) in TREM2. Our literature review reveals 16 TREM2 mutations causing early-onset dementia and bone lesions.<BR><B>CONCLUSIONS: </B>These findings, alongside previous research, elucidate the clinical spectrum of TREM2-related diseases, aiding accurate diagnosis and patient care. This knowledge is vital for understanding TREM2-dependent DAM and its involvement in the pathogenesis of neurodevelopmental disorders which can help to develop targeted therapies and improve outcomes for TREM2-affected individuals.