کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6803581 1433544 2016 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Novel PSEN1 mutations (H214N and R220P) associated with familial Alzheimer's disease identified by targeted exome sequencing
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Novel PSEN1 mutations (H214N and R220P) associated with familial Alzheimer's disease identified by targeted exome sequencing
چکیده انگلیسی
Autosomal dominant Alzheimer's disease (AD) is caused by mutations in amyloid precursor protein, presenilin 1 (PSEN1), and presenilin 2 genes and is mostly associated with early-onset form of AD (EOAD), whereas very few mutations were also found in late-onset AD (LOAD) cases. Because of the clinical overlapping between AD and other degenerative dementias such as frontotemporal dementias, a wide-spectrum genetic analysis should be envisaged in the differential diagnosis of this group of disorders. We used next-generation sequencing techniques to analyze 10 genes involved in dementia on a cohort of 20 EOAD and 20 LOAD cases. We found 5 rare coding variants (frequency <1%). PSEN1 H214N mutation, identified in a case of familial EOAD and PSEN1 R220P, found in a case of familial LOAD, are predicted to be pathogenic. These findings confirm the contribution of PSEN1 genetic variants also to LOAD, underlining the need of extending the genetic screening of presenilin mutations to LOAD patients. Two variants in microtubule-associated protein tau and 1 in progranulin appeared to be benign polymorphisms, showing no major contribution of these genes to AD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 40, April 2016, Pages 192.e7-192.e11
نویسندگان
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