May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
A Novel TIMP3 Mutation and in vivo Imaging of a Family With Sorsby Fundus Dystrophy
Author Affiliations & Notes
  • Z. Saihan
    Inherited Eye Diseases, Institute of Ophthalmology, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Z. Li
    Newcastle upon Tyne General Hospital, Welcome Laboratory for Biogerontology, Newcastle upon Tyne, United Kingdom
  • J. Rice
    The National Genetics Reference Laboratories, Manchester, United Kingdom
  • C.P. J. Blyth
    Ophthalmology, Royal Gwent Hospital, Newport, United Kingdom
  • S. Ramsden
    The National Genetics Reference Laboratories, Manchester, United Kingdom
  • G.C. Black
    Clinical Genetics, St. Mary's Hospital, Manchester, United Kingdom
  • N. McKie
    Newcastle upon Tyne General Hospital, Welcome Laboratory for Biogerontology, Newcastle upon Tyne, United Kingdom
  • A.R. Webster
    Inherited Eye Diseases, Institute of Ophthalmology, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Footnotes
    Commercial Relationships  Z. Saihan, None; Z. Li, None; J. Rice, None; C.P.J. Blyth, None; S. Ramsden, None; G.C. Black, None; N. McKie, None; A.R. Webster, None.
  • Footnotes
    Support  Foundation For Fighting Blindness
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 4610. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Z. Saihan, Z. Li, J. Rice, C.P. J. Blyth, S. Ramsden, G.C. Black, N. McKie, A.R. Webster; A Novel TIMP3 Mutation and in vivo Imaging of a Family With Sorsby Fundus Dystrophy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4610.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : To characterise and report a family with Sorsby’s fundus dystrophy (SFD) with a novel mutation in the TIMP3 gene

Methods: : The TIMP3 gene was analysed in a family and 3 mutation positive patients were studied with regard to their visual function and retinal imaging using colour fundus photography, scanning laser ophthalmoscope and optical coherence tomography. The mutant variant was expressed in ARPE19 and COS7 cells and assayed for inhibitory activity and oligomerisation.

Results: : A single base pair change (G>A 484) resulting in a glycine to a leucine at amino acid position 162 (E162K) was found to co segregate with the disease. This change was not found in a panel of 534 control chromosomes. The E162K change was affected by standard site–directed mutagenesis techniques in the wild–type protein sequence. Fundal retinal images show intrafamilial variability with regard to amount of drusenlike deposits throughout the retina as well as the amount of visible sub–retinal deposit. In all cases OCT–3 images demonstrate a hyper–reflective RPE–photoreceptor / choroid complex which may be due to the deposition of abnormal protein related to expression of the mutant TIMP–3 protein within Bruch’s membrane as previously reported in this condition.

Conclusions: : The E162K mutation is another cause of Sorsby fundus dystrophy. In vivo imaging techniques such as optical coherence tomography provide important information regarding the pathophysiology of SFD and could potentially be used as a diagnostic aid.

Keywords: retinal degenerations: hereditary • retinal degenerations: hereditary • genetics 
×
×

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.

×