Document Detail

Mutation in the gene GUCA1A, encoding guanylate cyclase-activating protein 1, causes cone, cone-rod, and macular dystrophy.
MedLine Citation:
PMID:  15953638     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To determine the underlying molecular genetic basis of a retinal dystrophy identified in a 4-generation family and to examine the phenotype and the degree of intrafamilial variability. DESIGN: Prospective case series. PARTICIPANTS: Six affected individuals from a nonconsanguineous British family. METHODS: Detailed ophthalmologic examination, color fundus photography, autofluorescence imaging, and electrophysiologic assessment were performed. Blood samples were taken for DNA extraction, and mutation screening of GUCA1A, the gene encoding guanylate cyclase-activating protein 1 (GCAP1), was undertaken. RESULTS: All affected subjects complained of mild photophobia and reduced central and color vision. Onset was between the third and fifth decade, with subsequent gradual deterioration of visual acuity and color vision. Visual acuity ranged between 6/9 and counting fingers. Color vision was either absent or markedly reduced along all 3 color axes. A range of macular appearances was seen, varying from mild retinal pigment epithelial disturbance to extensive atrophy. Electrophysiologic testing revealed a range of electrophysiologic abnormalities: isolated cone electroretinography abnormalities, reduced cone and rod responses (with cone loss greater than rod), and isolated macular dysfunction. The 4 coding exons of GUCA1A were screened for mutations in affected and unaffected family members. A single transition, A319G, causing a nonconservative missense substitution, Tyr99Cys, segregated uniquely in all affected subjects. CONCLUSIONS: The Tyr99Cys GUCA1A mutation has been previously shown to cause autosomal dominant progressive cone dystrophy. This is the first report of this mutation also causing both cone-rod dystrophy and isolated macular dysfunction. The phenotypic variation described here exemplifies the intrafamilial heterogeneity of retinal dysfunction that can be observed in persons harboring the same mutation and chromosomal segment.
Michel Michaelides; Susan E Wilkie; Sharon Jenkins; Graham E Holder; David M Hunt; Anthony T Moore; Andrew R Webster
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Ophthalmology     Volume:  112     ISSN:  1549-4713     ISO Abbreviation:  Ophthalmology     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-08-02     Completed Date:  2005-08-16     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7802443     Medline TA:  Ophthalmology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1442-7     Citation Subset:  IM    
Institute of Ophthalmology, University College London, London, United Kingdom.
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MeSH Terms
Calcium-Binding Proteins / genetics*
Color Perception Tests
Color Vision Defects / genetics
DNA Mutational Analysis
Guanylate Cyclase / genetics*
Guanylate Cyclase-Activating Proteins
Middle Aged
Mutation, Missense*
Photoreceptor Cells, Vertebrate / pathology*
Polymerase Chain Reaction
Prospective Studies
Retinal Degeneration / genetics*,  pathology
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/GUCA1A protein, human; 0/Guanylate Cyclase-Activating Proteins; EC Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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