Variable retinal phenotypes caused by mutations in the X-linked photopigment gene array.
OBJECTIVE
To examine the involvement of the long (L) and middle (M) wavelength-sensitive cone opsin genes in cone-dominated phenotypes.


METHODS
Clinical and molecular analyses included family history, color vision testing, full-field electroretinography (ERG), linkage analysis, and mutation detection.


RESULTS
Eighteen families were recruited that had X-linked retinal disease characterized by cone impairment in which affected males usually had nystagmus, reduced visual acuity, normal to subnormal rod ERG, and reduced or extinguished cone ERG responses. A search for mutations in the L-M pigment gene array revealed disease-causing mutations in six families. In two of them, novel mutations were identified: a large deletion affecting both opsin genes and a single L opsin gene harboring a likely pathogenic mutation, p.Val120Met. A third family carried a single hybrid gene with the p.Cys203Arg mutation. Patients from the three remaining families carried a single opsin gene harboring two similar rare haplotypes. Although the phenotype of members in one of the families was compatible with blue cone monochromacy (BCM), patients from the two other families, who shared an identical haplotype, had only reduced or even normal full-field cone ERGs, but maculopathy was evident.


CONCLUSIONS
Novel and known mutations affecting the L-M opsin gene array were identified in families with X-linked cone-dominated phenotypes. The results show that different mutations in this gene array can cause a variety of phenotypes, including BCM, cone dystrophy, and maculopathy. Males with X-linked cone-dominated diseases should be routinely analyzed for mutations in the L-M opsin gene array.
Mizrahi-Meissonnier
Liliana
L
Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Merin
Saul
S
Banin
Eyal
E
Sharon
Dror
D
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D003119:Color Perception Tests; D003117:Color Vision Defects / Q000235:genetics*; D055358:Cone Opsins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D050172:Genes, X-Linked; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009759:Nystagmus, Pathologic / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D012162:Retinal Degeneration / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields; D055815:Young Adult
D055358:Cone Opsins