Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2

Natalia Ogonowski, Hernando Santamaria-Garcia, Sandra Baez, Andrea Lopez, Andrés Laserna, Elkin Garcia-Cifuentes, Paola Ayala-Ramirez, Ignacio Zarante, Fernando Suarez-Obando, Pablo Reyes, Marcelo Kauffman, Nick Cochran, Michael Schulte, Daniel W. Sirkis, Salvatore Spina, Jennifer S. Yokoyama, Bruce L. Miller, Kenneth S. Kosik, Diana Matallana, Agustín Ibáñez

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

2 Citas (Scopus)


Background The triggering receptor expressed on myeloid cell 2 (TREM2) is a major regulator of neuroinflammatory processes in neurodegeneration. To date, the p.H157Y variant of TREM2 has been reported only in patients with Alzheimer's disease. Here, we report three patients with frontotemporal dementia (FTD) from three unrelated families with heterozygous p.H157Y variant of TREM2: two patients from Colombian families (study 1) and a third Mexican origin case from the USA (study 2). Methods To determine if the p.H157Y variant might be associated with a specific FTD presentation, we compared in each study the cases with age-matched, sex-matched and education-matched groups - a healthy control group (HC) and a group with FTD with neither TREM2 mutations nor family antecedents (Ng-FTD and Ng-FTD-MND). Results The two Colombian cases presented with early behavioural changes, greater impairments in general cognition and executive function compared with both HC and Ng-FTD groups. These patients also exhibited brain atrophy in areas characteristic of FTD. Furthermore, TREM2 cases showed increased atrophy compared with Ng-FTD in frontal, temporal, parietal, precuneus, basal ganglia, parahippocampal/hippocampal and cerebellar regions. The Mexican case presented with FTD and motor neuron disease (MND), showing grey matter reduction in basal ganglia and thalamus, and extensive TDP-43 type B pathology. Conclusion In all TREM2 cases, multiple atrophy peaks overlapped with the maximum peaks of TREM2 gene expression in crucial brain regions including frontal, temporal, thalamic and basal ganglia areas. These results provide the first report of an FTD presentation potentially associated with the p.H157Y variant with exacerbated neurocognitive impairments.

Idioma originalInglés
Páginas (desde-hasta)894-904
Número de páginas11
PublicaciónJournal of Medical Genetics
EstadoPublicada - 1 sep. 2023
Publicado de forma externa


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