A small gene sequencing panel realises a high diagnostic rate in patients with congenital nystagmus following basic phenotyping

Abstract Nystagmus is a disorder of uncontrolled eye movement and can occur as an isolated trait (idiopathic INS, IINS) or as part of multisystem disorders such as albinism, significant visual disorders or neurological disease. Eighty-one unrelated patients with nystagmus underwent routine ocular ph...

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Autores principales:	Luke O’Gorman, Chelsea S. Norman, Luke Michaels, Tutte Newall, Andrew H. Crosby, Christopher Mattocks, Angela J. Cree, Andrew J. Lotery, Emma L. Baple, J. Arjuna Ratnayaka, Diana Baralle, Helena Lee, Daniel Osborne, Fatima Shawkat, Jane Gibson, Sarah Ennis, Jay E. Self
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b9cd1a136f474a9fb875e2845e84278d
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spelling	oai:doaj.org-article:b9cd1a136f474a9fb875e2845e84278d2021-12-02T15:08:59ZA small gene sequencing panel realises a high diagnostic rate in patients with congenital nystagmus following basic phenotyping10.1038/s41598-019-49368-72045-2322https://doaj.org/article/b9cd1a136f474a9fb875e2845e84278d2019-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-49368-7https://doaj.org/toc/2045-2322Abstract Nystagmus is a disorder of uncontrolled eye movement and can occur as an isolated trait (idiopathic INS, IINS) or as part of multisystem disorders such as albinism, significant visual disorders or neurological disease. Eighty-one unrelated patients with nystagmus underwent routine ocular phenotyping using commonly available phenotyping methods and were grouped into four sub-cohorts according to the level of phenotyping information gained and their findings. DNA was extracted and sequenced using a broad utility next generation sequencing (NGS) gene panel. A clinical subpanel of genes for nystagmus/albinism was utilised and likely causal variants were prioritised according to methods currently employed by clinical diagnostic laboratories. We determine the likely underlying genetic cause for 43.2% of participants with similar yields regardless of prior phenotyping. This study demonstrates that a diagnostic workflow combining basic ocular phenotyping and a clinically available targeted NGS panel, can provide a high diagnostic yield for patients with infantile nystagmus, enabling access to disease specific management at a young age and reducing the need for multiple costly, often invasive tests. By describing diagnostic yield for groups of patients with incomplete phenotyping data, it also permits the subsequent design of ‘real-world’ diagnostic workflows and illustrates the changing role of genetic testing in modern diagnostic workflows for heterogeneous ophthalmic disorders.Luke O’GormanChelsea S. NormanLuke MichaelsTutte NewallAndrew H. CrosbyChristopher MattocksAngela J. CreeAndrew J. LoteryEmma L. BapleJ. Arjuna RatnayakaDiana BaralleHelena LeeDaniel OsborneFatima ShawkatJane GibsonSarah EnnisJay E. SelfNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-8 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luke O’Gorman Chelsea S. Norman Luke Michaels Tutte Newall Andrew H. Crosby Christopher Mattocks Angela J. Cree Andrew J. Lotery Emma L. Baple J. Arjuna Ratnayaka Diana Baralle Helena Lee Daniel Osborne Fatima Shawkat Jane Gibson Sarah Ennis Jay E. Self A small gene sequencing panel realises a high diagnostic rate in patients with congenital nystagmus following basic phenotyping
description	Abstract Nystagmus is a disorder of uncontrolled eye movement and can occur as an isolated trait (idiopathic INS, IINS) or as part of multisystem disorders such as albinism, significant visual disorders or neurological disease. Eighty-one unrelated patients with nystagmus underwent routine ocular phenotyping using commonly available phenotyping methods and were grouped into four sub-cohorts according to the level of phenotyping information gained and their findings. DNA was extracted and sequenced using a broad utility next generation sequencing (NGS) gene panel. A clinical subpanel of genes for nystagmus/albinism was utilised and likely causal variants were prioritised according to methods currently employed by clinical diagnostic laboratories. We determine the likely underlying genetic cause for 43.2% of participants with similar yields regardless of prior phenotyping. This study demonstrates that a diagnostic workflow combining basic ocular phenotyping and a clinically available targeted NGS panel, can provide a high diagnostic yield for patients with infantile nystagmus, enabling access to disease specific management at a young age and reducing the need for multiple costly, often invasive tests. By describing diagnostic yield for groups of patients with incomplete phenotyping data, it also permits the subsequent design of ‘real-world’ diagnostic workflows and illustrates the changing role of genetic testing in modern diagnostic workflows for heterogeneous ophthalmic disorders.
format	article
author	Luke O’Gorman Chelsea S. Norman Luke Michaels Tutte Newall Andrew H. Crosby Christopher Mattocks Angela J. Cree Andrew J. Lotery Emma L. Baple J. Arjuna Ratnayaka Diana Baralle Helena Lee Daniel Osborne Fatima Shawkat Jane Gibson Sarah Ennis Jay E. Self
author_facet	Luke O’Gorman Chelsea S. Norman Luke Michaels Tutte Newall Andrew H. Crosby Christopher Mattocks Angela J. Cree Andrew J. Lotery Emma L. Baple J. Arjuna Ratnayaka Diana Baralle Helena Lee Daniel Osborne Fatima Shawkat Jane Gibson Sarah Ennis Jay E. Self
author_sort	Luke O’Gorman
title	A small gene sequencing panel realises a high diagnostic rate in patients with congenital nystagmus following basic phenotyping
title_short	A small gene sequencing panel realises a high diagnostic rate in patients with congenital nystagmus following basic phenotyping
title_full	A small gene sequencing panel realises a high diagnostic rate in patients with congenital nystagmus following basic phenotyping
title_fullStr	A small gene sequencing panel realises a high diagnostic rate in patients with congenital nystagmus following basic phenotyping
title_full_unstemmed	A small gene sequencing panel realises a high diagnostic rate in patients with congenital nystagmus following basic phenotyping
title_sort	small gene sequencing panel realises a high diagnostic rate in patients with congenital nystagmus following basic phenotyping
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/b9cd1a136f474a9fb875e2845e84278d
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A small gene sequencing panel realises a high diagnostic rate in patients with congenital nystagmus following basic phenotyping

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