PURPOSE: Heterozygous mutations in the GUCY2D gene, which encodes the membrane-bound retinal guanylyl cyclase-1 protein (RetGC-1), have been shown to cause autosomal dominant inherited cone degeneration and cone-rod degeneration (adCD, adCRD). The present study was a comprehensive screening of the GUCY2D gene in 27 adCD and adCRD unrelated families of these rare disorders. METHODS: Mutation analysis was performed by direct sequencing as well as PCR and subsequent restriction length polymorphism analysis (PCR/RFLP). Haplotype analysis was performed in 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 showed that among the studied patients only two of the six analyzed p.R838C mutation carriers shared a common haplotype and that none of the p.R838H mutation carriers did. CONCLUSIONS: GUCY2D is a major gene responsible for progressive autosomal dominant cone degeneration. All identified mutations localize to codon 838. Haplotype analysis indicates that in most cases these mutations arise independently. Thus, codon 838 is likely to be a mutation hotspot in the GUCY2D gene.
PURPOSE: Heterozygous mutations in the GUCY2D gene, which encodes the membrane-bound retinal guanylyl cyclase-1 protein (RetGC-1), have been shown to cause autosomal dominant inherited cone degeneration and cone-rod degeneration (adCD, adCRD). The present study was a comprehensive screening of the GUCY2D gene in 27 adCD and adCRD unrelated families of these rare disorders. METHODS: Mutation analysis was performed by direct sequencing as well as PCR and subsequent restriction length polymorphism analysis (PCR/RFLP). Haplotype analysis was performed in 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 showed that among the studied patients only two of the six analyzed p.R838C mutation carriers shared a common haplotype and that none of the p.R838H mutation carriers did. CONCLUSIONS:GUCY2D is a major gene responsible for progressive autosomal dominant cone degeneration. All identified mutations localize to codon 838. Haplotype analysis indicates that in most cases these mutations arise independently. Thus, codon 838 is likely to be a mutation hotspot in the GUCY2D gene.
Authors: C L Tucker; S C Woodcock; R E Kelsell; V Ramamurthy; D M Hunt; J B Hurley Journal: Proc Natl Acad Sci U S A Date: 1999-08-03 Impact factor: 11.205
Authors: S E Wilkie; R J Newbold; E Deery; C E Walker; I Stinton; V Ramamurthy; J B Hurley; S S Bhattacharya; M J Warren; D M Hunt Journal: Hum Mol Genet Date: 2000-12-12 Impact factor: 6.150
Authors: X Liu; K Seno; Y Nishizawa; F Hayashi; A Yamazaki; H Matsumoto; T Wakabayashi; J Usukura Journal: Exp Eye Res Date: 1994-12 Impact factor: 3.467
Authors: Igor V Peshenko; Artur V Cideciyan; Alexander Sumaroka; Elena V Olshevskaya; Alexander Scholten; Seher Abbas; Karl-Wilhelm Koch; Samuel G Jacobson; Alexander M Dizhoor Journal: J Biol Chem Date: 2019-01-08 Impact factor: 5.157
Authors: Victor L Jensen; Nathan J Bialas; Sharon L Bishop-Hurley; Laurie L Molday; Katarzyna Kida; Phuong Anh T Nguyen; Oliver E Blacque; Robert S Molday; Michel R Leroux; Donald L Riddle Journal: PLoS Genet Date: 2010-11-24 Impact factor: 5.917