May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
Phenotypic Differences in Achromatopsia Due to CNGA3 and CNGB3 Mutations
Author Affiliations & Notes
  • N. W. Khan
    Ophthalmology, Univ of Michigan-Kellogg Eye Ctr, Ann Arbor, Michigan
  • B. Wissinger
    Molecular Genetics Lab, University Eye Hospital, Tuebingen, Germany
  • S. Kohl
    Molecular Genetics Lab, University Eye Hospital, Tuebingen, Germany
  • J. R. Heckenlively
    Ophthalmology, Univ of Michigan-Kellogg Eye Ctr, Ann Arbor, Michigan
  • Footnotes
    Commercial Relationships N.W. Khan, None; B. Wissinger, None; S. Kohl, None; J.R. Heckenlively, None.
  • Footnotes
    Support FFB to JRH; DFG Wi1189/6-3 to BW
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3694. doi:
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      N. W. Khan, B. Wissinger, S. Kohl, J. R. Heckenlively; Phenotypic Differences in Achromatopsia Due to CNGA3 and CNGB3 Mutations. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3694.

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

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Purpose:: CNGA3 encodes the α-subunits and CNGB3 encodes the ß-subunits of the cyclic nucleotide-gated channel on the cone photoreceptor plasma membrane. Mutations cause achromatopsia due to loss of cone function. We compared the CNGA3 and CNGB3 phenotypes in eleven affected subjects from ten families.

Methods:: CNGA3 mutations: 5 subjects, ages 4 months to 13 years from 4 families. CNGB3 mutations: 6 subjects, ages 8 months to 15 years, one 52 y/o, and one 31 y/o female carrier from 6 families. Examinations included acuity, color vision testing (CV), Goldmann visual fields (GVF), dark-adapted (DA) absolute thresholds, and OCT on older subjects; and ERG, and fundus ophthalmoscopy on all subjects.

Results:: In all affected subjects, acuity ranged from 20/50 to 20/200, and the two young (4 m/o and 8 m/o) subjects were able to fix and follow. GVFs were normal to mildly constricted. DA threshold sensitivity was normal. CV with Ishihara Plates ranged from seeing no plates to seeing all plates in both genotypes. All subjects including the carrier showed foveo-macular atrophy. The main difference between patients with CNGA3 and CNGB3 mutations was in the ERG. CNGA3: rod b-wave amplitude was reduced by 60% in 3 subjects, maximal stimulation a-wave was reduced by >50% in 3 subjects but b-wave was normal. Photopic b-wave and flicker were non-recordable in 3 subjects, and 2 subjects (including the 4 m/o) had residual responses. CNGB3: Rod b-wave amplitude was essentially normal except in two subjects (50% reduced). Maximal flash a-wave was >50% reduced in four subjects, while b-wave was normal resulting in a b/a wave ratio of 2.38 to 6.59 (Normal: 1.96 ± 0.38SD). All subjects had a residual flicker response and photopic b-wave amplitude that was 30% of normal, except the 52 y/o who had a residual 11 µV response. The CNGB3 carrier showed abnormal rod b-wave and a 75% loss in photopic b-wave and flicker.

Conclusions:: Mutations in CNGA3 and CNGB3 were equally prevalent in these 11 families, and have characteristics of a cone-rod dystrophy. Photopic b-wave is highly reduced in CNGA3 affected subjects, while all younger CNGB3 subjects had measurable cone b-wave responses. Abnormalities in rod b-wave and in the maximal response a-wave suggest impaired rod function in both genotypes. Relative preservation of b-wave amplitude with a reduction in a-wave amplitude suggests synaptic rewiring following partial loss of cone photoreceptors1.1. S. Haverkamp, et al., J Neurosci. 2006; 26:5248-55.

Keywords: degenerations/dystrophies • retinal degenerations: hereditary • genetics 

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