Discordant phenotypes in twins with infantile nystagmus
Abstract 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 di...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-82368-0 |
| _version_ | 1818681947254161408 |
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| author | Abdullah Aamir Helen J. Kuht Rebecca J. McLean Gail D. E. Maconachie Viral Sheth Basu Dawar Ravi Purohit Nicolas Sylvius Michael Hisaund Alina Zubcov-Iwantscheff Frank A. Proudlock Irene Gottlob Mervyn G. Thomas |
| author_facet | Abdullah Aamir Helen J. Kuht Rebecca J. McLean Gail D. E. Maconachie Viral Sheth Basu Dawar Ravi Purohit Nicolas Sylvius Michael Hisaund Alina Zubcov-Iwantscheff Frank A. Proudlock Irene Gottlob Mervyn G. Thomas |
| author_sort | Abdullah Aamir |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-17T10:11:02Z |
| format | Article |
| id | doaj.art-ef1b1a87fe7e4fe99e8c5be8c90a8040 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T10:11:02Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ef1b1a87fe7e4fe99e8c5be8c90a80402022-12-21T21:53:02ZengNature PortfolioScientific Reports2045-23222021-02-011111810.1038/s41598-021-82368-0Discordant phenotypes in twins with infantile nystagmusAbdullah Aamir0Helen J. Kuht1Rebecca J. McLean2Gail D. E. Maconachie3Viral Sheth4Basu Dawar5Ravi Purohit6Nicolas Sylvius7Michael Hisaund8Alina Zubcov-Iwantscheff9Frank A. Proudlock10Irene Gottlob11Mervyn G. Thomas12The University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSBThe University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSBThe University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSBThe University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSBThe University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSBThe University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSBThe University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSBNUCLEUS Genomics, Core Biotechnology Services, University of LeicesterThe University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSBPractice for OphthalmologyThe University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSBThe University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSBThe University of Leicester Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, RKCSBAbstract 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.https://doi.org/10.1038/s41598-021-82368-0 |
| spellingShingle | Abdullah Aamir Helen J. Kuht Rebecca J. McLean Gail D. E. Maconachie Viral Sheth Basu Dawar Ravi Purohit Nicolas Sylvius Michael Hisaund Alina Zubcov-Iwantscheff Frank A. Proudlock Irene Gottlob Mervyn G. Thomas Discordant phenotypes in twins with infantile nystagmus Scientific Reports |
| title | Discordant phenotypes in twins with infantile nystagmus |
| title_full | Discordant phenotypes in twins with infantile nystagmus |
| title_fullStr | Discordant phenotypes in twins with infantile nystagmus |
| title_full_unstemmed | Discordant phenotypes in twins with infantile nystagmus |
| title_short | Discordant phenotypes in twins with infantile nystagmus |
| title_sort | discordant phenotypes in twins with infantile nystagmus |
| url | https://doi.org/10.1038/s41598-021-82368-0 |
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