OBJECTIVE: To report a new genetic variant in the rhodopsin gene (RHO) associated with an unusual autosomal dominant retinal phenotype. METHODS: Detailed phenotypic characterization was performed on affected family members spanning 4 generations, including family history, best-corrected visual acuity, fundus examination, kinetic and static perimetry, full-field and multifocal electroretinography, fundus autofluorescence, and optical coherence tomography. For genetic testing, coding exons and flanking intronic regions of RHO were amplified with the use of polymerase chain reaction, purified, and sequenced. Cosegregation and control analysis were performed by direct sequencing of exon 3. Subsequent in silico analysis of the mutational consequence on protein function was undertaken. RESULTS: The onset of symptoms appeared in the fourth decade of life in this family, with moderate night blindness and asymmetrical visual loss. Affected members showed patchy areas of chorioretinal atrophy with decreased electroretinographic response amplitudes for both scotopic and photopic responses but no implicit time shift, consistent with restricted disease. A novel mutation in exon 3 of RHO was identified and represents a c.620T>A transition leading to a p.Met207Lys substitution. It cosegregated with this phenotype and was not identified in a control population. CONCLUSIONS: We report the phenotype-genotype correlation of an unusual autosomal dominant, late-onset restricted chorioretinal degeneration cosegregating with a novel RHO mutation, p.Met207Lys. A p.Met207Arg substitution has previously been reported to cause a distinct, generalized early-onset rod-cone dystrophy. Clinical Relevance These data outline the phenotypic variability associated with RHO mutations. Depending on the localization and the amino acid substitution, patients may show congenital stationary night blindness, rod-cone dystrophy, sector retinitis pigmentosa, or localized chorioretinal atrophy.
OBJECTIVE: To report a new genetic variant in the rhodopsin gene (RHO) associated with an unusual autosomal dominant retinal phenotype. METHODS: Detailed phenotypic characterization was performed on affected family members spanning 4 generations, including family history, best-corrected visual acuity, fundus examination, kinetic and static perimetry, full-field and multifocal electroretinography, fundus autofluorescence, and optical coherence tomography. For genetic testing, coding exons and flanking intronic regions of RHO were amplified with the use of polymerase chain reaction, purified, and sequenced. Cosegregation and control analysis were performed by direct sequencing of exon 3. Subsequent in silico analysis of the mutational consequence on protein function was undertaken. RESULTS: The onset of symptoms appeared in the fourth decade of life in this family, with moderate night blindness and asymmetrical visual loss. Affected members showed patchy areas of chorioretinal atrophy with decreased electroretinographic response amplitudes for both scotopic and photopic responses but no implicit time shift, consistent with restricted disease. A novel mutation in exon 3 of RHO was identified and represents a c.620T>A transition leading to a p.Met207Lys substitution. It cosegregated with this phenotype and was not identified in a control population. CONCLUSIONS: We report the phenotype-genotype correlation of an unusual autosomal dominant, late-onset restricted chorioretinal degeneration cosegregating with a novel RHO mutation, p.Met207Lys. A p.Met207Arg substitution has previously been reported to cause a distinct, generalized early-onset rod-cone dystrophy. Clinical Relevance These data outline the phenotypic variability associated with RHO mutations. Depending on the localization and the amino acid substitution, patients may show congenital stationary night blindness, rod-cone dystrophy, sector retinitis pigmentosa, or localized chorioretinal atrophy.
Authors: Eva Ramon; Arnau Cordomí; Mònica Aguilà; Sundaramoorthy Srinivasan; Xiaoyun Dong; Anthony T Moore; Andrew R Webster; Michael E Cheetham; Pere Garriga Journal: J Biol Chem Date: 2014-10-30 Impact factor: 5.157
Authors: Juliette Varin; Margaret M Reynolds; Nassima Bouzidi; Sarah Tick; Juliette Wohlschlegel; Ondine Becquart; Christelle Michiels; Olivier Dereure; Robert M Duvoisin; Catherine W Morgans; José-Alain Sahel; Quentin Samaran; Bernard Guillot; José S Pulido; Isabelle Audo; Christina Zeitz Journal: PLoS One Date: 2020-04-23 Impact factor: 3.240
Authors: Rola Ba-Abbad; Monique Leys; Xinjing Wang; Christina Chakarova; Naushin Waseem; Keren J Carss; F Lucy Raymond; Kinga M Bujakowska; Eric A Pierce; Omar A Mahroo; Moin D Mohamed; Graham E Holder; Marybeth Hummel; Gavin Arno; Andrew R Webster Journal: Invest Ophthalmol Vis Sci Date: 2018-10-01 Impact factor: 4.799