TREM2 Gene Compound Heterozygosity in Neurodegenerative Disorders.
J Alzheimers Dis
; 89(4): 1211-1219, 2022.
Article
em En
| MEDLINE
| ID: mdl-36031890
ABSTRACT
BACKGROUND:
Homozygous variants of the TREM2 and TYROBP genes have been shown to be causative for multiple bone cysts and neurodegeneration leading to progressive dementia (NHD, Nasu-Hakola disease).OBJECTIVE:
To determine if biallelic variants of these genes and/or oligogenic inheritance could be responsible for a wider spectrum of neurodegenerative conditions.METHODS:
We analyzed 52 genes associated with neurodegenerative disorders using targeted next generation sequencing in a selected group of 29 patients (nâ=â14 Alzheimer's disease, nâ=â8 frontotemporal dementia, nâ=â7 amyotrophic lateral sclerosis) carrying diverse already determined rare variants in exon 2 of TREM2. Molecular modeling was used to get an insight into the potential effects of the mutation.RESULTS:
We identified a novel mutation c.401_406delinsTCTAT; p.(Asp134Valfs*55) in exon 3 of TREM2 in an Alzheimer's disease patient also carrying the p.Arg62His TREM2 variant. Molecular modeling revealed that the identified mutation prevents anchoring of the TREM2 protein in the membrane, leaving the core of the Ig-like domain intact.CONCLUSION:
Our results expand the spectrum of neurodegenerative diseases, where the carriers of biallelic mutations in TREM2 have been described for Alzheimer's disease, and highlight the impact of variant burden in other genes on phenotypic heterogeneity.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteocondrodisplasias
/
Panencefalite Esclerosante Subaguda
/
Glicoproteínas de Membrana
/
Receptores Imunológicos
/
Doenças Neurodegenerativas
/
Doença de Alzheimer
Limite:
Humans
Idioma:
En
Revista:
J Alzheimers Dis
Assunto da revista:
GERIATRIA
/
NEUROLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Polônia