An unusual retinal phenotype associated with a novel mutation in RHO.
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.
Audo
Isabelle
I
Institut National de la Santé et de la Recherche Médicale, Paris, France. isabelle.audo@inserm.fr
Friedrich
Anne
A
Mohand-Saïd
Saddek
S
Lancelot
Marie-Elise
ME
Antonio
Aline
A
Moskova-Doumanova
Veselina
V
Poch
Olivier
O
Bhattacharya
Shomi
S
Sahel
José-Alain
JA
Zeitz
Christina
C
D000328:Adult; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005091:Exons / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D012243:Rhodopsin / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity; D014794:Visual Fields; D055815:Young Adult
D012243:Rhodopsin