May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Mutations in KCNJ13 Cause Autosomal Dominant Snowflake Vitreoretinal Degeneration
Author Affiliations & Notes
  • A. O. Edwards
    Ophthalmology, Mayo Clinic, Rochester, Minnesota
  • X. Jiao
    Ophthalmic Genetics and Visual Function Branch,
    National Eye Institute, NIH, Bethesda, Maryland
  • A. Li
    Ophthalmic Genetics and Visual Function Branch,
    National Eye Institute, NIH, Bethesda, Maryland
  • Y. V. Sergeev
    Ophthalmic Genetics and Visual Function Branch,
    National Eye Institute, NIH, Bethesda, Maryland
  • X. Ding
    Laboratory of Immunology, National Eye Institute, Bethesda, Maryland
  • A. K. Sharma
    Ophthalmology, Mayo Clinic, Rochester, Minnesota
  • C.-C. Chan
    Laboratory of Immunology,
    National Eye Institute, NIH, Bethesda, Maryland
  • I. Medina
    Inmed/Inserm and Mediterranean University, Parc Scientifique de Luminy, Marseille, France
  • J. F. Hejtmancik
    Ophthalmic Genetics and Visual Function Branch,
    National Eye Institute, NIH, Bethesda, Maryland
  • Footnotes
    Commercial Relationships  A.O. Edwards, None; X. Jiao, None; A. Li, None; Y.V. Sergeev, None; X. Ding, None; A.K. Sharma, None; C. Chan, None; I. Medina, None; J.F. Hejtmancik, None.
  • Footnotes
    Support  NIH Grant EY 014467; Research to Prevent Blindness; Mayo Clinic Foundation, Foundation Fighting Blindness
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2161. doi:https://doi.org/
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      A. O. Edwards, X. Jiao, A. Li, Y. V. Sergeev, X. Ding, A. K. Sharma, C.-C. Chan, I. Medina, J. F. Hejtmancik; Mutations in KCNJ13 Cause Autosomal Dominant Snowflake Vitreoretinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2161. doi: https://doi.org/.

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

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Abstract

Purpose: : Snowflake vitreoretinal degeneration (SVD, MIM 193230) is a developmental and progressive hereditary eye disorder that affects multiple tissues within the eye. Diagnostic features of SVD include fibrillar degeneration of the vitreous humor, early-onset cataract, minute crystalline deposits in the neurosensory retina, and retinal detachment.

Methods: : A genome-wide scan previously localized the genetic locus for SVD to a 20 Mb region flanked by D2S2158 and D2S2202. This region contains 59 genes, of which 20 were sequenced, disclosing a heterozygous mutation (484C>T, R162W) in KCNJ13, member 13 of subfamily J of the potassium inwardly-rectifying channel family in all affected individuals.

Results: : The mutation in KCNJ13, the gene encoding Kir7.1, was not present in unaffected family members and 210 control individuals. Kir7.1 localized to human retina and retinal pigment epithelium (RPE) and was especially prevalent in the internal limiting membrane adjacent to the vitreous body. Molecular modeling of this mutation predicted disruption of the structure of the potassium channel in the closed state located immediately adjacent to the cell membrane inner boundary. Functionally, unlike wild type Kir 7.1 whose overexpression in CHO-K1 cells line produces highly selective potassium current, overexpression of R162W mutant Kir7.1 produces a non-selective cation current that depolarizes transfected cells and increases their fragility.

Conclusions: : These results indicate that the KCNJ13 R162W mutation can cause SVD and further show that vitreoretinal degeneration can arise though mutations in genes whose products are not structural components of the vitreous.

Keywords: genetics • retinal degenerations: hereditary • vitreous 
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