Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy

Abstract The genetic background of dilated cardiomyopathy is highly heterogeneous, with close to 100 known genes and a number of candidates described to date. Nebulin-related-anchoring protein (NRAP) is an actin-binding cytoskeletal protein expressed predominantly in striated and cardiac muscles, an...

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Autores principales:	Grażyna T. Truszkowska, Zofia T. Bilińska, Angelika Muchowicz, Agnieszka Pollak, Anna Biernacka, Katarzyna Kozar-Kamińska, Piotr Stawiński, Piotr Gasperowicz, Joanna Kosińska, Tomasz Zieliński, Rafał Płoski
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6446ec4421834fc0878115d8121427e5
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spelling	oai:doaj.org-article:6446ec4421834fc0878115d8121427e52021-12-02T12:32:38ZHomozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy10.1038/s41598-017-03189-82045-2322https://doaj.org/article/6446ec4421834fc0878115d8121427e52017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03189-8https://doaj.org/toc/2045-2322Abstract The genetic background of dilated cardiomyopathy is highly heterogeneous, with close to 100 known genes and a number of candidates described to date. Nebulin-related-anchoring protein (NRAP) is an actin-binding cytoskeletal protein expressed predominantly in striated and cardiac muscles, and is involved in myofibrillar assembly in the foetal heart and in force transmission in the adult heart. The homozygous NRAP truncating variant (rs201084642), which is predicted to introduce premature stop codon into all NRAP isoforms, was revealed in the dilated cardiomyopathy patient using whole exome sequencing. The same genotype was detected in the asymptomatic proband’s brother. The expression of the NRAP protein was undetectable in the patient’s heart muscle by the Western blot. Genotyping for rs201084642 in the ethnically matched cohort of 231 dilated cardiomyopathy patients did not reveal any additional subjects with this variant. Our findings suggest that the biallelic loss-of-function mutation in NRAP could constitute a relatively rare, low-penetrance genetic risk factor for dilated cardiomyopathy.Grażyna T. TruszkowskaZofia T. BilińskaAngelika MuchowiczAgnieszka PollakAnna BiernackaKatarzyna Kozar-KamińskaPiotr StawińskiPiotr GasperowiczJoanna KosińskaTomasz ZielińskiRafał PłoskiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-5 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Grażyna T. Truszkowska Zofia T. Bilińska Angelika Muchowicz Agnieszka Pollak Anna Biernacka Katarzyna Kozar-Kamińska Piotr Stawiński Piotr Gasperowicz Joanna Kosińska Tomasz Zieliński Rafał Płoski Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy
description	Abstract The genetic background of dilated cardiomyopathy is highly heterogeneous, with close to 100 known genes and a number of candidates described to date. Nebulin-related-anchoring protein (NRAP) is an actin-binding cytoskeletal protein expressed predominantly in striated and cardiac muscles, and is involved in myofibrillar assembly in the foetal heart and in force transmission in the adult heart. The homozygous NRAP truncating variant (rs201084642), which is predicted to introduce premature stop codon into all NRAP isoforms, was revealed in the dilated cardiomyopathy patient using whole exome sequencing. The same genotype was detected in the asymptomatic proband’s brother. The expression of the NRAP protein was undetectable in the patient’s heart muscle by the Western blot. Genotyping for rs201084642 in the ethnically matched cohort of 231 dilated cardiomyopathy patients did not reveal any additional subjects with this variant. Our findings suggest that the biallelic loss-of-function mutation in NRAP could constitute a relatively rare, low-penetrance genetic risk factor for dilated cardiomyopathy.
format	article
author	Grażyna T. Truszkowska Zofia T. Bilińska Angelika Muchowicz Agnieszka Pollak Anna Biernacka Katarzyna Kozar-Kamińska Piotr Stawiński Piotr Gasperowicz Joanna Kosińska Tomasz Zieliński Rafał Płoski
author_facet	Grażyna T. Truszkowska Zofia T. Bilińska Angelika Muchowicz Agnieszka Pollak Anna Biernacka Katarzyna Kozar-Kamińska Piotr Stawiński Piotr Gasperowicz Joanna Kosińska Tomasz Zieliński Rafał Płoski
author_sort	Grażyna T. Truszkowska
title	Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy
title_short	Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy
title_full	Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy
title_fullStr	Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy
title_full_unstemmed	Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy
title_sort	homozygous truncating mutation in nrap gene identified by whole exome sequencing in a patient with dilated cardiomyopathy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6446ec4421834fc0878115d8121427e5
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Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy

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