Clinical variability and onset age modifiers in an extended Belgian GRN founder family.
Neurobiol Aging
; 67: 84-94, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-29653316
We previously reported a granulin (GRN) null mutation, originating from a common founder, in multiple Belgian families with frontotemporal dementia. Here, we used data of a 10-year follow-up study to describe in detail the clinical heterogeneity observed in this extended founder pedigree. We identified 85 patients and 40 unaffected mutation carriers, belonging to 29 branches of the founder pedigree. Most patients (74.4%) were diagnosed with frontotemporal dementia, while others had a clinical diagnosis of unspecified dementia, Alzheimer's dementia or Parkinson's disease. The observed clinical heterogeneity can guide clinical diagnosis, genetic testing, and counseling of mutation carriers. Onset of initial symptomatology is highly variable, ranging from age 45 to 80 years. Analysis of known modifiers, suggested effects of GRN rs5848, microtubule-associated protein tau H1/H2, and chromosome 9 open reading frame 72 G4C2 repeat length on onset age but explained only a minor fraction of the variability. Contrary, the extended GRN founder family is a valuable source for identifying other onset age modifiers based on exome or genome sequences. These modifiers might be interesting targets for developing disease-modifying therapies.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos e Proteínas de Sinalização Intercelular
/
Demência Frontotemporal
/
Estudos de Associação Genética
/
Mutação com Perda de Função
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article