June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Whole Genome Sequencing in Infantile Nystagmus
Author Affiliations & Notes
  • Mervyn George Thomas
    University of Leicester, Leicester England, United Kingdom
  • Gail Maconachie
    University of Leicester, Leicester England, United Kingdom
  • Rebecca McLean
    University of Leicester, Leicester England, United Kingdom
  • Helen Kuht
    University of Leicester, Leicester England, United Kingdom
  • Viral Sheth
    University of Leicester, Leicester England, United Kingdom
  • Michael Hisaund
    University of Leicester, Leicester England, United Kingdom
  • Swati Parida
    University of Leicester, Leicester England, United Kingdom
  • Abdullah Aamir
    University of Leicester, Leicester England, United Kingdom
  • Frank A Proudlock
    University of Leicester, Leicester England, United Kingdom
  • Irene Gottlob
    University of Leicester, Leicester England, United Kingdom
  • Footnotes
    Commercial Relationships   Mervyn Thomas, None; Gail Maconachie, None; Rebecca McLean, None; Helen Kuht, None; Viral Sheth, None; Michael Hisaund, None; Swati Parida, None; Abdullah Aamir, None; Frank Proudlock, None; Irene Gottlob, None
  • Footnotes
    Support  Fight for Sight, Medical Research Council, National Institute of Health Research
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2350. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Mervyn George Thomas, Gail Maconachie, Rebecca McLean, Helen Kuht, Viral Sheth, Michael Hisaund, Swati Parida, Abdullah Aamir, Frank A Proudlock, Irene Gottlob; Whole Genome Sequencing in Infantile Nystagmus. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2350.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Infantile nystagmus is a genetically heterogenous disorder often arising from mutations of genes expressed within the developing neural retina and brain. Previously we have developed a nystagmus gene panel showing high levels of diagnostic accuracy and in some instances revising the clinical diagnosis.1 We successfully nominated to study infantile nystagmus as part of the 100,000 genomes project and currently spearhead the 100,000 genomes sub-project on the molecular genetics of infantile nystagmus. Therefore, in this study, we explore the value of whole genome sequencing together with our nystagmus gene panel. Specifically, we investigate the role of mutations of FRMD7 in the molecular pathogenesis of idiopathic infantile nystagmus (IIN) in a cohort of patients in UK and identify any mutation hotspots.

Methods : This prospective study looked at a population of infantile nystagmus presenting to University Hospitals of Leicester Trust, United Kingdom and other UK clinical centres participating in the 100,000 genomes study. Diagnosis of IIN was made based on normal ocular pigmentation and normal electrodiagnostic tests (visual evoked potentials and electroretinogram). DNA was extracted from saliva or blood samples. Sequencing was performed either using our nystagmus gene panel or whole genome sequencing (WGS) as part of the 100,000 genomes study. Pilot results from 120 patients are presented as part of this study.

Results : 62 FRMD7 mutations were identified in total. This included 39 novel mutations. Comparison with previous mutation data revealed 2 mutation hotspots. This included the recurring missense mutation c. 796G>C resulting in substitution alanine to proline at codon position 266, predicted to destabilise the FERM-C domain of the FRMD7 protein. Similarly, we identified a nonsense mutation hotspot c.1003C>T resulting in a premature stop codon at position 335, predicted to result in nonsense mediated decay. WGS revealed several novel deep intronic mutations predicted to alter splicing.

Conclusions : We expand on the mutation spectrum of FRMD7. This is the first study to report mutation hotspots in the FRMD7 gene and explore the utility of WGS in nystagmus. This has direct significance when devising a genetic testing strategy for IIN. However, a significant proportion of patients remain unsolved therefore further analysis of the WGS data will facilitate novel gene discovery.

This is a 2020 ARVO Annual Meeting abstract.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×