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Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis
BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative disorders that share significant clinical, pathological and genetic overlap and are considered to represent different ends of a common disease spectrum. Mutations in Profilin1 have rec...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995330/ https://www.ncbi.nlm.nih.gov/pubmed/24309268 http://dx.doi.org/10.1136/jnnp-2013-306761 |
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author | Fratta, Pietro Charnock, James Collins, Toby Devoy, Anny Howard, Robin Malaspina, Andrea Orrell, Richard Sidle, Katie Clarke, Jan Shoai, Maryam Lu, Ching-hua Hardy, John Plagnol, Vincent Fisher, Elizabeth M C |
author_facet | Fratta, Pietro Charnock, James Collins, Toby Devoy, Anny Howard, Robin Malaspina, Andrea Orrell, Richard Sidle, Katie Clarke, Jan Shoai, Maryam Lu, Ching-hua Hardy, John Plagnol, Vincent Fisher, Elizabeth M C |
author_sort | Fratta, Pietro |
collection | PubMed |
description | BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative disorders that share significant clinical, pathological and genetic overlap and are considered to represent different ends of a common disease spectrum. Mutations in Profilin1 have recently been described as a rare cause of familial ALS. The PFN1 E117G missense variant has been described in familial and sporadic cases, and also found in controls, casting doubt on its pathogenicity. Interpretation of such variants represents a significant clinical-genetics challenge. OBJECTIVE AND RESULTS: Here, we combine a screen of a new cohort of 383 ALS patients with multiple-sequence datasets to refine estimates of the ALS and FTD risk associated with PFN1 E117G. Together, our cohorts add up to 5118 ALS and FTD cases and 13 089 controls. We estimate a frequency of E117G of 0.11% in controls and 0.25% in cases. Estimated odds after population stratification is 2.44 (95% CI 1.048 to ∞, Mantel-Haenszel test p=0.036). CONCLUSIONS: Our results show an association between E117G and ALS, with a moderate effect size. |
format | Online Article Text |
id | pubmed-3995330 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-39953302014-04-25 Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis Fratta, Pietro Charnock, James Collins, Toby Devoy, Anny Howard, Robin Malaspina, Andrea Orrell, Richard Sidle, Katie Clarke, Jan Shoai, Maryam Lu, Ching-hua Hardy, John Plagnol, Vincent Fisher, Elizabeth M C J Neurol Neurosurg Psychiatry Neurogenetics BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative disorders that share significant clinical, pathological and genetic overlap and are considered to represent different ends of a common disease spectrum. Mutations in Profilin1 have recently been described as a rare cause of familial ALS. The PFN1 E117G missense variant has been described in familial and sporadic cases, and also found in controls, casting doubt on its pathogenicity. Interpretation of such variants represents a significant clinical-genetics challenge. OBJECTIVE AND RESULTS: Here, we combine a screen of a new cohort of 383 ALS patients with multiple-sequence datasets to refine estimates of the ALS and FTD risk associated with PFN1 E117G. Together, our cohorts add up to 5118 ALS and FTD cases and 13 089 controls. We estimate a frequency of E117G of 0.11% in controls and 0.25% in cases. Estimated odds after population stratification is 2.44 (95% CI 1.048 to ∞, Mantel-Haenszel test p=0.036). CONCLUSIONS: Our results show an association between E117G and ALS, with a moderate effect size. BMJ Publishing Group 2014-05 2013-12-05 /pmc/articles/PMC3995330/ /pubmed/24309268 http://dx.doi.org/10.1136/jnnp-2013-306761 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 3.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Neurogenetics Fratta, Pietro Charnock, James Collins, Toby Devoy, Anny Howard, Robin Malaspina, Andrea Orrell, Richard Sidle, Katie Clarke, Jan Shoai, Maryam Lu, Ching-hua Hardy, John Plagnol, Vincent Fisher, Elizabeth M C Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis |
title | Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis |
title_full | Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis |
title_fullStr | Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis |
title_full_unstemmed | Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis |
title_short | Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis |
title_sort | profilin1 e117g is a moderate risk factor for amyotrophic lateral sclerosis |
topic | Neurogenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995330/ https://www.ncbi.nlm.nih.gov/pubmed/24309268 http://dx.doi.org/10.1136/jnnp-2013-306761 |
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