Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease.

Celeste Sassi; Rita Guerreiro; Raphael Gibbs; Jinhui Ding; Michelle K Lupton; Claire Troakes; Katie Lunnon; Safa Al-Sarraj; Chirstopher Medway; Jenny Lord; James Turton; David Mann; Julie Snowden; David Neary; Jeniffer Harris; Jose Bras; John F Powell; Andrew Singleton; John Hardy; Peter Passmore; David Craig; Janet Johnston; Bernadette McGuinness; Stephen Todd; Reinhard Heun; Heike Kölsch; Patrick G Kehoe; Nigel M Hooper; Emma R L C Vardy; David Mann; Stuart Pickering-Brown; Kristelle Brown; James Lowe; Kevin Morgan; A David Smith; Gordon Wilcock; Donald Warden; Clive Holmes

doi:10.1016/j.neurobiolaging.2014.04.026

Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease.

Celeste Sassi, Rita Guerreiro, Raphael Gibbs, Jinhui Ding, Michelle K Lupton, Claire Troakes, Katie Lunnon, Safa Al-Sarraj, Chirstopher Medway, Jenny Lord, James Turton, David Mann, Julie Snowden, David Neary, Jeniffer Harris, Jose Bras, John F Powell, Andrew Singleton, John Hardy, Peter Passmore (Collaborator)David Craig (Collaborator), Janet Johnston (Collaborator), Bernadette McGuinness (Collaborator), Stephen Todd (Collaborator), Reinhard Heun (Collaborator), Heike Kölsch (Collaborator), Patrick G Kehoe (Collaborator), Nigel M Hooper (Collaborator), Emma R L C Vardy (Collaborator), David Mann (Collaborator), Stuart Pickering-Brown (Collaborator), Kristelle Brown (Collaborator), James Lowe (Collaborator), Kevin Morgan (Collaborator), A David Smith (Collaborator), Gordon Wilcock (Collaborator), Donald Warden (Collaborator), Clive Holmes (Collaborator)

Division of Neuroscience

Research output: Contribution to journal › Article › peer-review

Abstract

Early-onset Alzheimer's disease (EOAD) represents 1%-2% of the Alzheimer's disease (AD) cases, and it is generally characterized by a positive family history and a rapidly progressive symptomatology. Rare coding and fully penetrant variants in amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the only causative mutations reported for autosomal dominant AD. Thus, in this study we used exome sequencing data to rapidly screen rare coding variability in APP, PSEN1, and PSEN2, in a British cohort composed of 47 unrelated EOAD cases and 179 elderly controls, neuropathologically proven. We report 2 novel and likely pathogenic variants in PSEN1 (p.L166V and p.S230R). A comprehensive catalog of rare pathogenic variants in the AD Mendelian genes is pivotal for a premortem diagnosis of autosomal dominant EOAD and for the differential diagnosis with other early onset dementias such as frontotemporal dementia (FTD) and Creutzfeldt-Jakob disease (CJD).

Original language	English
Pages (from-to)	2422e13-e16
Journal	Neurobiology of Aging
Volume	35
Issue number	10
DOIs	https://doi.org/10.1016/j.neurobiolaging.2014.04.026
Publication status	Published - Oct 2014

Keywords

APP
British cohort
Early-onset Alzheimer's disease
PSEN1
PSEN2

Research Beacons, Institutes and Platforms

Dementia@Manchester

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.neurobiolaging.2014.04.026

Cite this

Sassi, C., Guerreiro, R., Gibbs, R., Ding, J., Lupton, M. K., Troakes, C., Lunnon, K., Al-Sarraj, S., Medway, C., Lord, J., Turton, J., Mann, D., Snowden, J., Neary, D., Harris, J., Bras, J., Powell, J. F., Singleton, A., Hardy, J., ... Holmes, C. (2014). Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease. Neurobiology of Aging, 35(10), 2422e13-e16. https://doi.org/10.1016/j.neurobiolaging.2014.04.026

@article{528b7144efa849e5bf0da5373f133038,

title = "Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease.",

abstract = "Early-onset Alzheimer's disease (EOAD) represents 1%-2% of the Alzheimer's disease (AD) cases, and it is generally characterized by a positive family history and a rapidly progressive symptomatology. Rare coding and fully penetrant variants in amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the only causative mutations reported for autosomal dominant AD. Thus, in this study we used exome sequencing data to rapidly screen rare coding variability in APP, PSEN1, and PSEN2, in a British cohort composed of 47 unrelated EOAD cases and 179 elderly controls, neuropathologically proven. We report 2 novel and likely pathogenic variants in PSEN1 (p.L166V and p.S230R). A comprehensive catalog of rare pathogenic variants in the AD Mendelian genes is pivotal for a premortem diagnosis of autosomal dominant EOAD and for the differential diagnosis with other early onset dementias such as frontotemporal dementia (FTD) and Creutzfeldt-Jakob disease (CJD).",

keywords = "APP, British cohort, Early-onset Alzheimer's disease, PSEN1, PSEN2",

author = "Celeste Sassi and Rita Guerreiro and Raphael Gibbs and Jinhui Ding and Lupton, {Michelle K} and Claire Troakes and Katie Lunnon and Safa Al-Sarraj and Chirstopher Medway and Jenny Lord and James Turton and David Mann and Julie Snowden and David Neary and Jeniffer Harris and Jose Bras and Powell, {John F} and Andrew Singleton and John Hardy and Peter Passmore and David Craig and Janet Johnston and Bernadette McGuinness and Stephen Todd and Reinhard Heun and Heike K{\"o}lsch and Kehoe, {Patrick G} and Hooper, {Nigel M} and Vardy, {Emma R L C} and David Mann and Stuart Pickering-Brown and Kristelle Brown and James Lowe and Kevin Morgan and Smith, {A David} and Gordon Wilcock and Donald Warden and Clive Holmes",

note = "089698, Wellcome Trust, United KingdomG-1107, Parkinson's UK, United KingdomG0701441, Medical Research Council, United KingdomP50 AG016574, NIA NIH HHS, United StatesR01 AG18023, NIA NIH HHS, United StatesU01 AG006786, NIA NIH HHS, United StatesWT089698, Wellcome Trust, United KingdomZO1 AG000950-10, NIA NIH HHS, United States",

year = "2014",

month = oct,

doi = "10.1016/j.neurobiolaging.2014.04.026",

language = "English",

volume = "35",

pages = "2422e13--e16",

journal = "Neurobiology of Aging",

issn = "1558-1497",

publisher = "Elsevier BV",

number = "10",

}

Sassi, C, Guerreiro, R, Gibbs, R, Ding, J, Lupton, MK, Troakes, C, Lunnon, K, Al-Sarraj, S, Medway, C, Lord, J, Turton, J, Mann, D, Snowden, J, Neary, D, Harris, J, Bras, J, Powell, JF, Singleton, A, Hardy, J, Passmore, P, Craig, D, Johnston, J, McGuinness, B, Todd, S, Heun, R, Kölsch, H, Kehoe, PG, Hooper, NM, Vardy, ERLC, Mann, D, Pickering-Brown, S, Brown, K, Lowe, J, Morgan, K, Smith, AD, Wilcock, G, Warden, D & Holmes, C 2014, 'Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease.', Neurobiology of Aging, vol. 35, no. 10, pp. 2422e13-e16. https://doi.org/10.1016/j.neurobiolaging.2014.04.026

TY - JOUR

T1 - Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease.

AU - Sassi, Celeste

AU - Guerreiro, Rita

AU - Gibbs, Raphael

AU - Ding, Jinhui

AU - Lupton, Michelle K

AU - Troakes, Claire

AU - Lunnon, Katie

AU - Al-Sarraj, Safa

AU - Medway, Chirstopher

AU - Lord, Jenny

AU - Turton, James

AU - Mann, David

AU - Snowden, Julie

AU - Neary, David

AU - Harris, Jeniffer

AU - Bras, Jose

AU - Powell, John F

AU - Singleton, Andrew

AU - Hardy, John

A2 - Passmore, Peter

A2 - Craig, David

A2 - Johnston, Janet

A2 - McGuinness, Bernadette

A2 - Todd, Stephen

A2 - Heun, Reinhard

A2 - Kölsch, Heike

A2 - Kehoe, Patrick G

A2 - Hooper, Nigel M

A2 - Vardy, Emma R L C

A2 - Mann, David

A2 - Pickering-Brown, Stuart

A2 - Brown, Kristelle

A2 - Lowe, James

A2 - Morgan, Kevin

A2 - Smith, A David

A2 - Wilcock, Gordon

A2 - Warden, Donald

A2 - Holmes, Clive

N1 - 089698, Wellcome Trust, United KingdomG-1107, Parkinson's UK, United KingdomG0701441, Medical Research Council, United KingdomP50 AG016574, NIA NIH HHS, United StatesR01 AG18023, NIA NIH HHS, United StatesU01 AG006786, NIA NIH HHS, United StatesWT089698, Wellcome Trust, United KingdomZO1 AG000950-10, NIA NIH HHS, United States

PY - 2014/10

Y1 - 2014/10

N2 - Early-onset Alzheimer's disease (EOAD) represents 1%-2% of the Alzheimer's disease (AD) cases, and it is generally characterized by a positive family history and a rapidly progressive symptomatology. Rare coding and fully penetrant variants in amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the only causative mutations reported for autosomal dominant AD. Thus, in this study we used exome sequencing data to rapidly screen rare coding variability in APP, PSEN1, and PSEN2, in a British cohort composed of 47 unrelated EOAD cases and 179 elderly controls, neuropathologically proven. We report 2 novel and likely pathogenic variants in PSEN1 (p.L166V and p.S230R). A comprehensive catalog of rare pathogenic variants in the AD Mendelian genes is pivotal for a premortem diagnosis of autosomal dominant EOAD and for the differential diagnosis with other early onset dementias such as frontotemporal dementia (FTD) and Creutzfeldt-Jakob disease (CJD).

AB - Early-onset Alzheimer's disease (EOAD) represents 1%-2% of the Alzheimer's disease (AD) cases, and it is generally characterized by a positive family history and a rapidly progressive symptomatology. Rare coding and fully penetrant variants in amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the only causative mutations reported for autosomal dominant AD. Thus, in this study we used exome sequencing data to rapidly screen rare coding variability in APP, PSEN1, and PSEN2, in a British cohort composed of 47 unrelated EOAD cases and 179 elderly controls, neuropathologically proven. We report 2 novel and likely pathogenic variants in PSEN1 (p.L166V and p.S230R). A comprehensive catalog of rare pathogenic variants in the AD Mendelian genes is pivotal for a premortem diagnosis of autosomal dominant EOAD and for the differential diagnosis with other early onset dementias such as frontotemporal dementia (FTD) and Creutzfeldt-Jakob disease (CJD).

KW - APP

KW - British cohort

KW - Early-onset Alzheimer's disease

KW - PSEN1

KW - PSEN2

U2 - 10.1016/j.neurobiolaging.2014.04.026

DO - 10.1016/j.neurobiolaging.2014.04.026

M3 - Article

C2 - 24880964

SN - 1558-1497

VL - 35

SP - 2422e13-e16

JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 10

ER -

Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease.

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

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