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The C9orf72 expansion is associated with accelerated respiratory function decline in a large Amyotrophic Lateral Sclerosis cohort
Introduction: The C9orf72 hexanucleotide repeat expansion is causal in amyotrophic lateral sclerosis (ALS) and has a negative effect on prognosis. The C9orf72 repeat expansion has been associated with an accelerated deterioration of respiratory function and survival in a cohort of 372 Portuguese pat...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
F1000 Research Limited
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140774/ https://www.ncbi.nlm.nih.gov/pubmed/32296747 http://dx.doi.org/10.12688/hrbopenres.12940.1 |
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author | Rooney, James Murray, Deirdre Campion, Anna Moloney, Hannah Tattersall, Rachel Doherty, Mark Hammond, Michaela Heverin, Mark McLaughlin, Russell Hardiman, Orla |
author_facet | Rooney, James Murray, Deirdre Campion, Anna Moloney, Hannah Tattersall, Rachel Doherty, Mark Hammond, Michaela Heverin, Mark McLaughlin, Russell Hardiman, Orla |
author_sort | Rooney, James |
collection | PubMed |
description | Introduction: The C9orf72 hexanucleotide repeat expansion is causal in amyotrophic lateral sclerosis (ALS) and has a negative effect on prognosis. The C9orf72 repeat expansion has been associated with an accelerated deterioration of respiratory function and survival in a cohort of 372 Portuguese patients. Methods: Cases presenting to the Irish ALS clinic with both longitudinal occluded sniff nasal inspiratory pressure (SNIP) and C9orf72 testing were including in the study. Clinical variables and survival characteristics of these patients were collected. Joint longitudinal and time to event models were constructed to explore the longitudinal characteristics of the cohort by C9orf72 status. Results: In total, 630 cases were included, of which 58 (9.2%) carried the C9orf72 repeat expansion. Plots of the longitudinal trend after joint modelling revealed that those carrying the expansion had worse respiratory function throughout the course of their disease than those without. The ALS Functional Rating Scale-revised (ALSFRS-R) respiratory sub-score did not distinguish C9orf72 normal from expanded cases. Furthermore, modelling by site of onset and gender sub-groups revealed that this difference was greatest in male spinal onset cases. Joint models further indicated that occluded SNIP values were of prognostic importance. Conclusions: Our results confirm findings from Portugal that the C9orf72 repeat expansion is associated with accelerated respiratory function decline. Analysis via joint models indicate that respiratory function is of prognostic importance and may explain previous observations of poorer prognosis in male spinal onset patients carrying the C9orf72 expansion. |
format | Online Article Text |
id | pubmed-7140774 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | F1000 Research Limited |
record_format | MEDLINE/PubMed |
spelling | pubmed-71407742020-04-14 The C9orf72 expansion is associated with accelerated respiratory function decline in a large Amyotrophic Lateral Sclerosis cohort Rooney, James Murray, Deirdre Campion, Anna Moloney, Hannah Tattersall, Rachel Doherty, Mark Hammond, Michaela Heverin, Mark McLaughlin, Russell Hardiman, Orla HRB Open Res Research Article Introduction: The C9orf72 hexanucleotide repeat expansion is causal in amyotrophic lateral sclerosis (ALS) and has a negative effect on prognosis. The C9orf72 repeat expansion has been associated with an accelerated deterioration of respiratory function and survival in a cohort of 372 Portuguese patients. Methods: Cases presenting to the Irish ALS clinic with both longitudinal occluded sniff nasal inspiratory pressure (SNIP) and C9orf72 testing were including in the study. Clinical variables and survival characteristics of these patients were collected. Joint longitudinal and time to event models were constructed to explore the longitudinal characteristics of the cohort by C9orf72 status. Results: In total, 630 cases were included, of which 58 (9.2%) carried the C9orf72 repeat expansion. Plots of the longitudinal trend after joint modelling revealed that those carrying the expansion had worse respiratory function throughout the course of their disease than those without. The ALS Functional Rating Scale-revised (ALSFRS-R) respiratory sub-score did not distinguish C9orf72 normal from expanded cases. Furthermore, modelling by site of onset and gender sub-groups revealed that this difference was greatest in male spinal onset cases. Joint models further indicated that occluded SNIP values were of prognostic importance. Conclusions: Our results confirm findings from Portugal that the C9orf72 repeat expansion is associated with accelerated respiratory function decline. Analysis via joint models indicate that respiratory function is of prognostic importance and may explain previous observations of poorer prognosis in male spinal onset patients carrying the C9orf72 expansion. F1000 Research Limited 2019-09-26 /pmc/articles/PMC7140774/ /pubmed/32296747 http://dx.doi.org/10.12688/hrbopenres.12940.1 Text en Copyright: © 2019 Rooney J et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Rooney, James Murray, Deirdre Campion, Anna Moloney, Hannah Tattersall, Rachel Doherty, Mark Hammond, Michaela Heverin, Mark McLaughlin, Russell Hardiman, Orla The C9orf72 expansion is associated with accelerated respiratory function decline in a large Amyotrophic Lateral Sclerosis cohort |
title | The C9orf72 expansion is associated with accelerated respiratory function decline in a large Amyotrophic Lateral Sclerosis cohort |
title_full | The C9orf72 expansion is associated with accelerated respiratory function decline in a large Amyotrophic Lateral Sclerosis cohort |
title_fullStr | The C9orf72 expansion is associated with accelerated respiratory function decline in a large Amyotrophic Lateral Sclerosis cohort |
title_full_unstemmed | The C9orf72 expansion is associated with accelerated respiratory function decline in a large Amyotrophic Lateral Sclerosis cohort |
title_short | The C9orf72 expansion is associated with accelerated respiratory function decline in a large Amyotrophic Lateral Sclerosis cohort |
title_sort | c9orf72 expansion is associated with accelerated respiratory function decline in a large amyotrophic lateral sclerosis cohort |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140774/ https://www.ncbi.nlm.nih.gov/pubmed/32296747 http://dx.doi.org/10.12688/hrbopenres.12940.1 |
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