PURPOSE. Heterozygous mutations in the GUCY2D gene, whichencodes the membrane-bound retinal guanylyl cyclase-1 protein(RetGC-1), have been shown to cause autosomal dominantinherited cone degeneration and cone–rod degeneration(adCD, adCRD). The present study was a comprehensivescreening of the GUCY2D gene in 27 adCD and adCRD unrelatedfamilies of these rare disorders.METHODS. Mutation analysis was performed by direct sequencingas well as PCR and subsequent restriction length polymorphismanalysis (PCR/RFLP). Haplotype analysis was performedin selected patients by using microsatellite markers.RESULTS. GUCY2D gene mutations were identified in 11 (40%)of 27 patients, and all mutations clustered to codon 838,including two known and one novel missense mutation:p.R838C, p.R838H, and p.R838G. Haplotype analysis showedthat among the studied patients only two of the six analyzedp.R838C mutation carriers shared a common haplotype andthat none of the p.R838H mutation carriers did.CONCLUSIONS. GUCY2D is a major gene responsible for progressiveautosomal dominant cone degeneration. All identified mutationslocalize to codon 838. Haplotype analysis indicates thatin most cases these mutations arise independently. Thus,codon 838 is likely to be a mutation hotspot in the GUCY2Dgene.
|Rivista||INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE|
|Stato di pubblicazione||Published - 2008|
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