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 Publisher Pubmed



Gilani N^{1, 2} ; Bitarafan F³ ; Ozaslan M¹ ; Asheim S³ ; Heidari M⁴ ; Garshasbi M⁵
Source: Molecular Genetics and Genomic Medicine Published:2024

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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. © 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.