Age-related penetrance of the C9orf72 repeat expansion

Abstract A pathogenic hexanucleotide repeat expansion within the C9orf72 gene has been identified as the major cause of two neurodegenerative syndromes, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This mutation is known to have incomplete penetrance, with some patients dev...

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Autores principales:	Natalie A. Murphy, Karissa C. Arthur, Pentti J. Tienari, Henry Houlden, Adriano Chiò, Bryan J. Traynor
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c16f885d26e849e1b7ccd204b86e2ac3
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spelling	oai:doaj.org-article:c16f885d26e849e1b7ccd204b86e2ac32021-12-02T12:32:17ZAge-related penetrance of the C9orf72 repeat expansion10.1038/s41598-017-02364-12045-2322https://doaj.org/article/c16f885d26e849e1b7ccd204b86e2ac32017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02364-1https://doaj.org/toc/2045-2322Abstract A pathogenic hexanucleotide repeat expansion within the C9orf72 gene has been identified as the major cause of two neurodegenerative syndromes, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This mutation is known to have incomplete penetrance, with some patients developing disease in their twenties and a small portion of carriers surviving to their ninth decade without developing symptoms. Describing penetrance by age among C9orf72 carriers and identifying parameters that alter onset age are essential to better understanding this locus and to enhance predictive counseling. To do so, data from 1,170 individuals were used to model penetrance. Our analysis showed that the penetrance was incomplete and age-dependent. Additionally, familial and sporadic penetrance did not significantly differ from one another; ALS cases exhibited earlier age of onset than FTD cases; and individuals with spinal-onset exhibited earlier age of onset than those with bulbar-onset. The older age of onset among female cases in general, and among female bulbar-onset cases in particular, was the most striking finding, and there may be an environmental, lifestyle, or hormonal factor that is influencing these penetrance patterns. These results will have important applications for future clinical research, the identification of disease modifiers, and genetic counseling.Natalie A. MurphyKarissa C. ArthurPentti J. TienariHenry HouldenAdriano ChiòBryan J. TraynorNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-7 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Natalie A. Murphy Karissa C. Arthur Pentti J. Tienari Henry Houlden Adriano Chiò Bryan J. Traynor Age-related penetrance of the C9orf72 repeat expansion
description	Abstract A pathogenic hexanucleotide repeat expansion within the C9orf72 gene has been identified as the major cause of two neurodegenerative syndromes, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This mutation is known to have incomplete penetrance, with some patients developing disease in their twenties and a small portion of carriers surviving to their ninth decade without developing symptoms. Describing penetrance by age among C9orf72 carriers and identifying parameters that alter onset age are essential to better understanding this locus and to enhance predictive counseling. To do so, data from 1,170 individuals were used to model penetrance. Our analysis showed that the penetrance was incomplete and age-dependent. Additionally, familial and sporadic penetrance did not significantly differ from one another; ALS cases exhibited earlier age of onset than FTD cases; and individuals with spinal-onset exhibited earlier age of onset than those with bulbar-onset. The older age of onset among female cases in general, and among female bulbar-onset cases in particular, was the most striking finding, and there may be an environmental, lifestyle, or hormonal factor that is influencing these penetrance patterns. These results will have important applications for future clinical research, the identification of disease modifiers, and genetic counseling.
format	article
author	Natalie A. Murphy Karissa C. Arthur Pentti J. Tienari Henry Houlden Adriano Chiò Bryan J. Traynor
author_facet	Natalie A. Murphy Karissa C. Arthur Pentti J. Tienari Henry Houlden Adriano Chiò Bryan J. Traynor
author_sort	Natalie A. Murphy
title	Age-related penetrance of the C9orf72 repeat expansion
title_short	Age-related penetrance of the C9orf72 repeat expansion
title_full	Age-related penetrance of the C9orf72 repeat expansion
title_fullStr	Age-related penetrance of the C9orf72 repeat expansion
title_full_unstemmed	Age-related penetrance of the C9orf72 repeat expansion
title_sort	age-related penetrance of the c9orf72 repeat expansion
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c16f885d26e849e1b7ccd204b86e2ac3
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Age-related penetrance of the C9orf72 repeat expansion

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