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Ophthalmic Molecular Genetics
August 2010

An Unusual Retinal Phenotype Associated With a Novel Mutation in RHO

Author Affiliations

Author Affiliations: Institut National de la Santé et de la Recherche Médicale (INSERM), U968, (Drs Audo, Mohand-Saïd, Bhattacharya, Sahel, and Zeitz and Mss Lancelot, Antonio, and Moskova-Doumanova), Institut de la Vision, Université Pierre et Marie Curie 6, UMR_S 968 (Drs Audo, Mohand-Saïd, Bhattacharya, Sahel, and Zeitz and Mss Lancelot, Antonio, and Moskova-Doumanova), CNRS, UMR_7210 (Drs Audo, Mohand-Saïd, Bhattacharya, Sahel, and Zeitz and Mss Lancelot, Antonio, and Moskova-Doumanova), and Centre de Référence Maladies rares “dystrophies rétiniennes d’origine génétique,” Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503 (Drs Audo, Mohand-Saïd, and Sahel), Paris, France; Department of Molecular Genetics, Institute of Ophthalmology, London, England (Drs Audo and Bhattacharya); and Laboratoire de Bioinformatique et de Génomique Intégratives, Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR7104, Illkirch, France (Drs Friedrich and Poch).



Arch Ophthalmol. 2010;128(8):1036-1045. doi:10.1001/archophthalmol.2010.162

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.