Analysis of Fibroblast Growth Factor 14 (FGF14) structural variants reveals the genetic basis of the early onset nystagmus locus NYS4 and variable ataxia.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
27
04
2022
accepted:
14
09
2022
revised:
02
09
2022
pubmed:
8
10
2022
medline:
11
3
2023
entrez:
7
10
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36207621
doi: 10.1038/s41431-022-01197-5
pii: 10.1038/s41431-022-01197-5
pmc: PMC9995494
doi:
Substances chimiques
fibroblast growth factor 14
0
Fibroblast Growth Factors
62031-54-3
Integrin beta1
0
ITGBL1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
353-359Informations de copyright
© 2022. The Author(s).
Références
Clark R, Blundell J, Dunn MJ, Erichsen JT, Giardini ME, Gottlob I, et al. The potential and value of objective eye tracking in the ophthalmology clinic. Eye. 2019;33:1200–2.
doi: 10.1038/s41433-019-0417-z
pubmed: 30962545
pmcid: 7005882
Osborne D, Theodorou M, Lee H, Ranger M, Hedley-Lewis M, Shawkat F, et al. Supranuclear eye movements and nystagmus in children: A review of the literature and guide to clinical examination, interpretation of findings and age-appropriate norms. Eye. 2019;33:261–73.
doi: 10.1038/s41433-018-0216-y
pubmed: 30353137
Self JE, Dunn MJ, Erichsen JT, Gottlob I, Griffiths HJ, Harris C, et al. Management of nystagmus in children: a review of the literature and current practice in UK specialist services. Eye. 2020;34:1515–34.
doi: 10.1038/s41433-019-0741-3
pubmed: 31919431
pmcid: 7608566
van Swieten JC, Brusse E, de Graaf BM, Krieger E, van de Graaf R, de Koning I, et al. A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebellar ataxia [corrected]. Am J Hum Genet. 2003;72:191–9.
doi: 10.1086/345488
pubmed: 12489043
Piarroux J, Riant F, Humbertclaude V, Remerand G, Hadjadj J, Rejou F, et al. FGF14-related episodic ataxia: delineating the phenotype of Episodic Ataxia type 9. Ann Clin Transl Neurol. 2020;7:565–72.
doi: 10.1002/acn3.51005
pubmed: 32162847
pmcid: 7187715
Choquet K, La Piana R, Brais B. A novel frameshift mutation in FGF14 causes an autosomal dominant episodic ataxia. Neurogenetics 2015;16:233–6.
doi: 10.1007/s10048-014-0436-7
pubmed: 25566820
Harris CM, Walker J, Shawkat F, Wilson J, Russell-Eggitt I. Eye movements in a familial vestibulocerebellar disorder. Neuropediatrics 1993;24:117–22.
doi: 10.1055/s-2008-1071526
pubmed: 8355816
Ragge NK, Hartley C, Dearlove AM, Walker J, Russell-Eggitt I, Harris CM. Familial vestibulocerebellar disorder maps to chromosome 13q31-q33: a new nystagmus locus. J Med Genet. 2003;40:37–41.
doi: 10.1136/jmg.40.1.37
pubmed: 12525540
pmcid: 1735258
Cameron DL, Schröder J, Penington JS, Do H, Molania R, Dobrovic A, et al. GRIDSS: sensitive and specific genomic rearrangement detection using positional de Bruijn graph assembly. Genome Res. 2017;27:2050–60.
doi: 10.1101/gr.222109.117
pubmed: 29097403
pmcid: 5741059
Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020;22:245–57.
doi: 10.1038/s41436-019-0686-8
pubmed: 31690835
Di ReJ, Wadsworth PA, Laezza F. Intracellular Fibroblast Growth Factor 14: Emerging risk factor for brain disorders. Front Cell Neurosci. 2017;11:103.
doi: 10.3389/fncel.2017.00103
Tucker ME, Kalb FM, Escobar LF Infant Spinocerebellar Ataxia Type 27: Early Presentation Due To a 13q33.1 Microdeletion Involving the FGF14 Gene. J Genet Syndr Gene Ther. 2013;4:1–3.
Coebergh JA, Fransen van de Putte DE, Snoeck IN, Ruivenkamp C, van Haeringen A, Smit LM. A new variable phenotype in spinocerebellar ataxia 27 (SCA 27) caused by a deletion in the FGF14 gene. Eur J Paediatr Neurol. 2014;18:413–5.
doi: 10.1016/j.ejpn.2013.10.006
pubmed: 24252256
Planes M, Rooryck C, Vuillaume ML, Besnard L, Bouron J, Lacombe D, et al. SCA27 is a cause of early-onset ataxia and developmental delay. Eur J Paediatr Neurol. 2015;19:271–3.
doi: 10.1016/j.ejpn.2014.11.013
pubmed: 25530029
Paucar M, Lundin J, Alshammari T, Bergendal Å, Lindefeldt M, Alshammari M, et al. Broader phenotypic traits and widespread brain hypometabolism in spinocerebellar ataxia 27. J Intern Med. 2020;288:103–15.
doi: 10.1111/joim.13052
pubmed: 32112487
Amado A, Blanco MO, Repáraz-Andrade A. Spinocerebellar Ataxia 27: clinical phenotype of twin sisters with FGF14 deletion. Neuropediatrics 2017;48:131.
doi: 10.1055/s-0037-1598110
pubmed: 28192817
Zech M, Boesch S, Škorvánek M, Necpál J, Švantnerová J, Wagner M, et al. Clinically relevant copy-number variants in exome sequencing data of patients with dystonia. Parkinsonism Relat Disord. 2021;84:129–34.
doi: 10.1016/j.parkreldis.2021.02.013
pubmed: 33611074
Groth CL, Berman BD. Spinocerebellar Ataxia 27: a review and characterization of an evolving phenotype. Tremor Other Hyperkinet Mov. 2018;8:534.
doi: 10.5334/tohm.436
Self J, Mercer C, Boon EM, Murugavel M, Shawkat F, Hammans S, et al. Infantile nystagmus and late onset ataxia associated with a CACNA1A mutation in the intracellular loop between s4 and s5 of domain 3. Eye. 2009;23:2251–5.
doi: 10.1038/eye.2008.389
pubmed: 19182766
Casteels I, Harris CM, Shawkat F, Taylor D. Nystagmus in infancy. Br J Ophthalmol. 1992;76:434–7.
doi: 10.1136/bjo.76.7.434
pubmed: 1627515
pmcid: 504306