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Analysis of Fibroblast Growth Factor 14 (FGF14) structural variants reveals the genetic basis of the early onset nystagmus locus NYS4 and variable ataxia

Analysis of Fibroblast Growth Factor 14 (FGF14) structural variants reveals the genetic basis of the early onset nystagmus locus NYS4 and variable ataxia
Analysis of Fibroblast Growth Factor 14 (FGF14) structural variants reveals the genetic basis of the early onset nystagmus locus NYS4 and variable ataxia
Nystagmus (involuntary, rhythmical eye movements) can arise due to sensory eye defects, in association with neurological disorders or as an isolated condition. We identified a family with early onset nystagmus and additional neurological features carrying a partial duplication of FGF14, a gene associated with spinocerebellar ataxia type 27 (SCA27) and episodic ataxia. Detailed eye movement analysis revealed oculomotor anomalies strikingly similar to those reported in a previously described four-generation family with early onset nystagmus and linkage to a region on chromosome 13q31.3-q33.1 (NYS4). Since FGF14 lies within NYS4, we revisited the original pedigree using whole genome sequencing, identifying a 161kb heterozygous deletion disrupting FGF14 and ITGBL1 in the affected individuals, suggesting an FGF14-related condition. Therefore, our study reveals the genetic variant underlying NYS4, expands the spectrum of pathogenic FGF14 variants, and highlights the importance of screening FGF14 in apparently isolated early onset nystagmus.
1018-4813
Ceroni, Fabiola
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Osborne, Daniel
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Clokie, Samuel
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Bax, Doreen
a48a8006-f6fa-4e61-85de-a7ed62579abd
Cassidy, Emma
3f88029c-2b62-406c-ad65-cb9e52e2811a
Dunn, Matt
fab9d2ea-2428-4c2d-8c72-7c07515b7dfc
Harris, Chris M.
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Self, Jay
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Ragge, Nicola K.
226c769b-4091-48f9-94c3-2e933e6d6fdf
Ceroni, Fabiola
40f410a9-a3b2-43cd-9f64-0d485e0f217a
Osborne, Daniel
d42306f4-65ba-4e3f-8402-6663f3963ee7
Clokie, Samuel
8d81a7f0-e6c0-4a9e-bded-1e2069bbf788
Bax, Doreen
a48a8006-f6fa-4e61-85de-a7ed62579abd
Cassidy, Emma
3f88029c-2b62-406c-ad65-cb9e52e2811a
Dunn, Matt
fab9d2ea-2428-4c2d-8c72-7c07515b7dfc
Harris, Chris M.
7b9af8e6-065a-4090-8b7a-6d5510270a25
Self, Jay
0f6efc58-ae24-4667-b8d6-6fafa849e389
Ragge, Nicola K.
226c769b-4091-48f9-94c3-2e933e6d6fdf

Ceroni, Fabiola, Osborne, Daniel, Clokie, Samuel, Bax, Doreen, Cassidy, Emma, Dunn, Matt, Harris, Chris M., Self, Jay and Ragge, Nicola K. (2022) Analysis of Fibroblast Growth Factor 14 (FGF14) structural variants reveals the genetic basis of the early onset nystagmus locus NYS4 and variable ataxia. European Journal of Human Genetics. (doi:10.1038/s41431-022-01197-5).

Record type: Article

Abstract

Nystagmus (involuntary, rhythmical eye movements) can arise due to sensory eye defects, in association with neurological disorders or as an isolated condition. We identified a family with early onset nystagmus and additional neurological features carrying a partial duplication of FGF14, a gene associated with spinocerebellar ataxia type 27 (SCA27) and episodic ataxia. Detailed eye movement analysis revealed oculomotor anomalies strikingly similar to those reported in a previously described four-generation family with early onset nystagmus and linkage to a region on chromosome 13q31.3-q33.1 (NYS4). Since FGF14 lies within NYS4, we revisited the original pedigree using whole genome sequencing, identifying a 161kb heterozygous deletion disrupting FGF14 and ITGBL1 in the affected individuals, suggesting an FGF14-related condition. Therefore, our study reveals the genetic variant underlying NYS4, expands the spectrum of pathogenic FGF14 variants, and highlights the importance of screening FGF14 in apparently isolated early onset nystagmus.

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Accepted/In Press date: 20 September 2022
Published date: 7 October 2022

Identifiers

Local EPrints ID: 471072
URI: http://eprints.soton.ac.uk/id/eprint/471072
ISSN: 1018-4813
PURE UUID: 805bafc1-bda0-4416-a2b0-ade7a90e0b08
ORCID for Jay Self: ORCID iD orcid.org/0000-0002-1030-9963

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Date deposited: 25 Oct 2022 16:41
Last modified: 26 Oct 2022 01:39

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Contributors

Author: Fabiola Ceroni
Author: Daniel Osborne
Author: Samuel Clokie
Author: Doreen Bax
Author: Emma Cassidy
Author: Matt Dunn
Author: Chris M. Harris
Author: Jay Self ORCID iD
Author: Nicola K. Ragge

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