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Title: Development and clinical utility of a novel diagnostic nystagmus gene panel using targeted next-generation sequencing
Authors: Thomas, Mervyn G.
Maconachie, Gail D. E.
Sheth, Viral
McLean, Rebecca J.
Gottlob, Irene
First Published: 5-Apr-2017
Publisher: Nature Publishing Group for European Society of Human Genetics
Citation: European Journal of Human Genetics, 2017, 25, pp. 725-734
Abstract: Infantile nystagmus (IN) is a genetically heterogeneous disorder arising from variants of genes expressed within the developing retina and brain. IN presents a diagnostic challenge and patients often undergo numerous investigations. We aimed to develop and assess the utility of a next-generation sequencing (NGS) panel to enhance the diagnosis of IN. We identified 336 genes associated with IN from the literature and OMIM. NimbleGen Human custom array was used to enrich the target genes and sequencing was performed using HiSeq2000. Using reference genome material (NA12878), we show the sensitivity (98.5%) and specificity (99.9%) of the panel. Fifteen patients with familial IN were sequenced using the panel. Two authors were masked to the clinical diagnosis. We identified variants in 12/15 patients in the following genes: FRMD7 (n=3), CACNA1F (n=2), TYR (n=5), CRYBA1 (n=1) and TYRP1 (n=1). In 9/12 patients, the clinical diagnosis was consistent with the genetic diagnosis. In 3/12 patients, the results from the genetic diagnoses (TYR, CRYBA1 and TYRP1 variants) enabled revision of clinical diagnoses. In 3/15 patients, we were unable to determine a genetic diagnosis. In one patient, copy number variation analysis revealed a FRMD7 deletion. This is the first study establishing the clinical utility of a diagnostic NGS panel for IN. We show that the panel has high sensitivity and specificity. The genetic information from the panel will lead to personalised diagnosis and management of IN and enable accurate genetic counselling. This will allow development of a new clinical care pathway for IN.European Journal of Human Genetics advance online publication, 5 April 2017; doi:10.1038/ejhg.2017.44.
DOI Link: 10.1038/ejhg.2017.44
ISSN: 1018-4813
eISSN: 1476-5438
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Neuroscience, Psychology and Behaviour

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