Analysis of fibroblast growth factor 14 (fgf14) structural variants reveals the genetic basis of the early onset nystagmus locus nyS4 and variable ataxia

Ceroni, Fabiola, Osborne, Daniel, Clokie, Samuel, Bax, Dorine A., Cassidy, Emma J., Dunn, Matt J. ORCID: https://orcid.org/0000-0002-0295-2182, Harris, Christopher M., Self, Jay E. and Ragge, Nicola K. 2023. 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 31 , pp. 353-359. 10.1038/s41431-022-01197-5

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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 161 kb 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Optometry and Vision Sciences
Publisher:	Springer Nature
ISSN:	1018-4813
Funders:	Baillie Gifford; Microphthalmia, Anophthalmia and Coloboma Support (MACS) (www.macs.org.uk); Oxford Brookes University Health Innovation Fund (HEIF) and the Gift of Sight Charity
Date of First Compliant Deposit:	17 October 2022
Date of Acceptance:	14 September 2022
Last Modified:	15 May 2023 18:39
URI:	https://orca.cardiff.ac.uk/id/eprint/153325

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