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

Doc Ophthalmol. 2014 Feb;128(1):59-67. doi: 10.1007/s10633-013-9420-z. Epub 2013 Dec 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Disease Progression
  • Electroretinography
  • Exons / genetics
  • Female
  • Fundus Oculi
  • Guanylate Cyclase-Activating Proteins / genetics*
  • Humans
  • Introns / genetics
  • Male
  • Mutation, Missense*
  • Pedigree
  • Photoreceptor Cells, Vertebrate / pathology
  • Polymerase Chain Reaction
  • Retinitis Pigmentosa / diagnosis
  • Retinitis Pigmentosa / genetics*
  • Visual Acuity / physiology

Substances

  • GUCA1A protein, human
  • Guanylate Cyclase-Activating Proteins