کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6802912 | 1433517 | 2018 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Clinical variability and onset age modifiers in an extended Belgian GRN founder family
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
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 80Â 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 67, July 2018, Pages 84-94
Journal: Neurobiology of Aging - Volume 67, July 2018, Pages 84-94
نویسندگان
Eline Wauters, Sara Van Mossevelde, Kristel Sleegers, Julie van der Zee, Sebastiaan Engelborghs, Anne Sieben, Rik Vandenberghe, Stéphanie Philtjens, Marleen Van den Broeck, Karin Peeters, Ivy Cuijt, Wouter De Coster, Tim Van Langenhove, Patrick Santens,