Novel PSEN1 mutations (H214N and R220P) associated with familial Alzheimer’s disease identified by targeted exome sequencing

Abstract Autosomal dominant Alzheimer’s disease (AD) is caused by mutations in amyloid precursor protein ( APP ), presenilin1 ( PSEN1 ) and presenilin 2 ( PSEN2 ) genes and is mostly associated with early-onset form of AD (EOAD), although very few mutations were also found in late-onset AD (LOAD) ca...

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Published in:Neurobiology of aging 2016-04, Vol.40, p.192.e7-192.e11
Main Authors: Piccoli, Elena, Rossi, Giacomina, Rossi, Tommaso, Pelliccioni, Giuseppe, D’Amato, Ilaria, Tagliavini, Fabrizio, Di Fede, Giuseppe
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Alzheimer Disease - genetics
Alzheimer's disease
Exome - genetics
Female
Genetic Association Studies
Humans
Internal Medicine
Male
Middle Aged
Mutation
Neurology
Presenilin-1 - genetics
PSEN1
Sequence Analysis, DNA - methods
Targeted exome sequencing
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description Abstract Autosomal dominant Alzheimer’s disease (AD) is caused by mutations in amyloid precursor protein ( APP ), presenilin1 ( PSEN1 ) and presenilin 2 ( PSEN2 ) genes and is mostly associated with early-onset form of AD (EOAD), although very few mutations were also found in late-onset AD (LOAD) cases. Since 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 ten genes involved in dementia on a cohort of 20 EOAD and 20 LOAD cases. We found five rare coding variants (frequency
doi_str_mv 10.1016/j.neurobiolaging.2016.01.134
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Since 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 ten genes involved in dementia on a cohort of 20 EOAD and 20 LOAD cases. We found five rare coding variants (frequency &lt;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. 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Since 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 ten genes involved in dementia on a cohort of 20 EOAD and 20 LOAD cases. We found five rare coding variants (frequency &lt;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. 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subjects Adult
Aged
Aged, 80 and over
Alzheimer Disease - genetics
Alzheimer's disease
Exome - genetics
Female
Genetic Association Studies
Humans
Internal Medicine
Male
Middle Aged
Mutation
Neurology
Presenilin-1 - genetics
PSEN1
Sequence Analysis, DNA - methods
Targeted exome sequencing
title Novel PSEN1 mutations (H214N and R220P) associated with familial Alzheimer’s disease identified by targeted exome sequencing
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