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Discordant phenotypes in twins with infantile nystagmus

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posted on 03.03.2021, 10:15 by A Aamir, HJ Kuht, RJ McLean, GDE Maconachie, V Sheth, B Dawar, R Purohit, N Sylvius, M Hisaund, A Zubcov-Iwantscheff, FA Proudlock, I Gottlob, MG Thomas
Infantile nystagmus (IN) may result from aetiologies including albinism and FRMD7 mutations. IN has low prevalence, and twins with IN are rare. Whilst discordant presentation has been previously reported for IN, we present for the first time the comprehensive assessment of diagnostically discordant monozygotic twins. From a cohort of over 2000 patients, we identified twins and triplets discordant for nystagmus. Using next-generation sequencing, high-resolution infra-red pupil tracking and optical coherence tomography, we characterised differences in genotype and phenotype. Monozygotic twins (n = 1), dizygotic twins (n = 3) and triplets (n = 1) were included. The monozygotic twins had concordant TYR variants. No causative variants were identified in the triplets. Dizygotic twins had discordant variants in TYR, OCA2 and FRMD7. One unaffected co-twin demonstrated sub-clinical nystagmus. Foveal hypoplasia (FH) was noted in four of five probands. Both co-twins of the monozygotic pair and triplets displayed FH. In three families, at least one parent had FH without nystagmus. FH alone may be insufficient to develop nystagmus. Whilst arrested optokinetic reflex pathway development is implicated in IN, discordant twins raise questions regarding where differences in development have arisen. In unaffected monozygotes therefore, genetic variants may predispose to oculomotor instability, with variable expressivity possibly responsible for the discordance observed.

Funding

Medical Research Council (MRC), London, UK (Grant Nos. MR/J004189/1, MRC/N004566/1 and MC_PC_17171), Ulverscroft Foundation and Fight for Sight (Grant Ref: 5009/5010 and 24NN181). MGT is supported by the NIHR (CL-2017-11-003).

History

Citation

Sci Rep 11, 2826 (2021). https://doi.org/10.1038/s41598-021-82368-0

Author affiliation

Department of Neuroscience, Psychology and Behaviour, College of Life Sciences

Version

VoR (Version of Record)

Published in

Scientific Reports

Volume

11

Issue

1

Pagination

2826

Publisher

Springer Science and Business Media LLC

issn

2045-2322

eissn

2045-2322

Acceptance date

18/01/2021

Copyright date

2021

Available date

02/02/2021

Spatial coverage

England

Language

eng

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