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Disease progression in autosomal dominant cone–rod dystrophy caused by a novel mutation (D100G) in the GUCA1A gene

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Abstract

Purpose

To document longitudinal fundus autofluorescence (FAF) and electroretinogram (ERG) findings in a family with cone–rod dystrophy (CRD) caused by a novel missense mutation (D100G) in the GUCA1A gene.

Methods

Observational case series.

Results

Three family members 26–49 years old underwent complete clinical examinations. In all patients, funduscopic findings showed intraretinal pigment migration, loss of neurosensory retinal pigment epithelium, and macular atrophy. FAF imaging revealed the presence of a progressive hyperautofluorescent ring around a hypoautofluorescent center corresponding to macular atrophy. Full-field ERGs showed a more severe loss of cone than rod function in each patient. Thirty-hertz flicker responses fell far below normal limits. Longitudinal FAF and ERG findings in one patient suggested progressive CRD. Two more advanced patients exhibited reduced rod response consistent with disease stage. Direct sequencing of the GUCA1A gene revealed a new missense mutation, p.Asp100Gly (D100G), in each patient.

Conclusion

Patients with autosomal dominant CRD caused by a D100G mutation in GUCA1A exhibit progressive vision loss early within the first decade of life identifiable by distinct ERG characteristics and subsequent genetic testing.

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Abbreviations

CD:

Cone dystrophy

CRD:

Cone–rod dystrophy

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Acknowledgments

Supported in part by Grants from the National Eye Institute/NIH EY021163, EY019861, EY018213, EY019007 (Core Support for Vision Research), National Cancer Institute Core [5P30CA013696] and unrestricted funds from Research to Prevent Blindness, New York, NY, USA. S.H.T. is a member of the RD-CURE Consortium and is supported by Tistou and Charlotte Kerstan Foundation, the National Institute of Health [R01EY018213], the Research to Prevent Blindness Physician-Scientist Award, the Barbara and Donald Jonas Family Fund, the Schneeweiss Stem Cell Fund, New York State [N09G-302], the Foundation Fighting Blindness New York Regional Research Center Grant [C-NY05-0705-0312], the Joel Hoffman Fund, Professor Gertrude Rothschild Stem Cell Foundation, and Gebroe Family Foundation.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Columbia University, New York, NY, USA

    Eva Nong, Winston Lee, Joanna E. Merriam, Rando Allikmets & Stephen H. Tsang

  2. Department of Pathology and Cell Biology, Columbia University, New York, NY, USA

    Rando Allikmets & Stephen H. Tsang

  3. Bernard and Shirlee Brown Glaucoma Laboratory, Edward S. Harkness Eye Institute, 160 Fort Washington Ave, Research Annex, Room 513, New York, NY, 10032, USA

    Stephen H. Tsang

Authors
  1. Eva Nong
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  2. Winston Lee
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  3. Joanna E. Merriam
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  4. Rando Allikmets
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  5. Stephen H. Tsang
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Corresponding author

Correspondence to Stephen H. Tsang.

Electronic supplementary material

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Pedigree for the affected family illustrates the dominant inheritance (PDF 13 kb)

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Nong, E., Lee, W., Merriam, J.E. et al. Disease progression in autosomal dominant cone–rod dystrophy caused by a novel mutation (D100G) in the GUCA1A gene. Doc Ophthalmol 128, 59–67 (2014). https://doi.org/10.1007/s10633-013-9420-z

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