VAPB and C9orf72 mutations in 1 familial amyotrophic lateral sclerosis patient

Marka van Blitterswijk; Michael A. van Es; Max Koppers; Wouter van Rheenen; Jelena Medic; Helenius J. Schelhaas; Anneke J. van der Kooi; Marianne de Visser; Jan H. Veldink; Leonard H. van den Berg

doi:10.1016/j.neurobiolaging.2012.07.004

VAPB and C9orf72 mutations in 1 familial amyotrophic lateral sclerosis patient

Marka van Blitterswijk, Michael A. van Es, Max Koppers, Wouter van Rheenen, Jelena Medic, Helenius J. Schelhaas, Anneke J. van der Kooi, Marianne de Visser, Jan H. Veldink, Leonard H. van den Berg

Neuroscience

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

38 Scopus citations

Abstract

Previously, we have reported amyotrophic lateral sclerosis (ALS) families with multiple mutations in major ALS-associated genes. These findings provided evidence for an oligogenic basis of ALS. In our present study, we screened a cohort of 755 sporadic ALS patients, 111 familial ALS patients (97 families), and 765 control subjects of Dutch descent for mutations in vesicle-associated membrane protein B (VAPB). We have identified 1 novel VAPB mutation (p.V234I) in a familial ALS patient known to have a chromosome 9 open reading frame 72 (C9orf72) repeat expansion. This p.V234I mutation was absent in control subjects, located in a region with high evolutionary conservation, and predicted to have damaging effects. Taken together, these findings provide additional evidence for an oligogenic basis of ALS.

Original language	English (US)
Pages (from-to)	2950.e1-2950.e4
Journal	Neurobiology of aging
Volume	33
Issue number	12
DOIs	https://doi.org/10.1016/j.neurobiolaging.2012.07.004
State	Published - Dec 2012

Keywords

Amyotrophic lateral sclerosis
C9orf72
Familial ALS
Genetics
Motor neuron disease
VAPB

ASJC Scopus subject areas

Clinical Neurology
Geriatrics and Gerontology
Aging
General Neuroscience
Developmental Biology

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10.1016/j.neurobiolaging.2012.07.004

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title = "VAPB and C9orf72 mutations in 1 familial amyotrophic lateral sclerosis patient",

abstract = "Previously, we have reported amyotrophic lateral sclerosis (ALS) families with multiple mutations in major ALS-associated genes. These findings provided evidence for an oligogenic basis of ALS. In our present study, we screened a cohort of 755 sporadic ALS patients, 111 familial ALS patients (97 families), and 765 control subjects of Dutch descent for mutations in vesicle-associated membrane protein B (VAPB). We have identified 1 novel VAPB mutation (p.V234I) in a familial ALS patient known to have a chromosome 9 open reading frame 72 (C9orf72) repeat expansion. This p.V234I mutation was absent in control subjects, located in a region with high evolutionary conservation, and predicted to have damaging effects. Taken together, these findings provide additional evidence for an oligogenic basis of ALS.",

keywords = "Amyotrophic lateral sclerosis, C9orf72, Familial ALS, Genetics, Motor neuron disease, VAPB",

author = "{van Blitterswijk}, Marka and {van Es}, {Michael A.} and Max Koppers and {van Rheenen}, Wouter and Jelena Medic and Schelhaas, {Helenius J.} and {van der Kooi}, {Anneke J.} and {de Visser}, Marianne and Veldink, {Jan H.} and {van den Berg}, {Leonard H.}",

note = "Funding Information: This work was supported by the VSB fonds, The Thierry Latran Foundation, Prinses Beatrix Fonds, Catharijne Stichting, H. Kersten and M. Kersten, J.R. van Dijk, the Adessium Foundation, and European Community's Health Seventh Framework Program (FP7/2007-2013) under grant agreement number 259867 . ",

year = "2012",

month = dec,

doi = "10.1016/j.neurobiolaging.2012.07.004",

language = "English (US)",

volume = "33",

pages = "2950.e1--2950.e4",

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AU - van Blitterswijk, Marka

AU - van Es, Michael A.

AU - Koppers, Max

AU - van Rheenen, Wouter

AU - Medic, Jelena

AU - Schelhaas, Helenius J.

AU - van der Kooi, Anneke J.

AU - de Visser, Marianne

AU - Veldink, Jan H.

AU - van den Berg, Leonard H.

N1 - Funding Information: This work was supported by the VSB fonds, The Thierry Latran Foundation, Prinses Beatrix Fonds, Catharijne Stichting, H. Kersten and M. Kersten, J.R. van Dijk, the Adessium Foundation, and European Community's Health Seventh Framework Program (FP7/2007-2013) under grant agreement number 259867 .

PY - 2012/12

Y1 - 2012/12

N2 - Previously, we have reported amyotrophic lateral sclerosis (ALS) families with multiple mutations in major ALS-associated genes. These findings provided evidence for an oligogenic basis of ALS. In our present study, we screened a cohort of 755 sporadic ALS patients, 111 familial ALS patients (97 families), and 765 control subjects of Dutch descent for mutations in vesicle-associated membrane protein B (VAPB). We have identified 1 novel VAPB mutation (p.V234I) in a familial ALS patient known to have a chromosome 9 open reading frame 72 (C9orf72) repeat expansion. This p.V234I mutation was absent in control subjects, located in a region with high evolutionary conservation, and predicted to have damaging effects. Taken together, these findings provide additional evidence for an oligogenic basis of ALS.

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KW - C9orf72

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VAPB and C9orf72 mutations in 1 familial amyotrophic lateral sclerosis patient

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