Abstract
Blue cone monochromatism (BCM) is an X-linked recessive cone dysfunction disorder caused by mutations in the OPN1LW/OPN1MW gene cluster, encoding long (L)- and middle (M)-wavelength-sensitive cone opsins. Here, we report on the unusual clinical presentation of BCM caused by a novel mutation in the OPN1LW gene in a young man. We describe in detail the phenotype of the proband, and the subclinical morpho-functional anomalies shown by his carrier mother. At a clinical level, the extensive functional evaluation demonstrated in the proband the M/L cone affection and the sparing of S-cone function, distinctive findings of BCM. Interestingly, spectral-domain optical coherence tomography showed the presence of foveal hypoplasia with focal irregularities of the ellipsoid layer in the foveal area, reported to be associated with some cases of cone-rod dystrophy and achromatopsia. At a molecular level, we identified the novel mutation c.427T > C p.(Ser143Pro) in the OPN1LW gene and the common missense mutation c.607T > C (p.Cys203Arg) in the OPN1MW gene. In addition, we discovered the c.768-2_769delAGTT splicing variant in the GPR143 gene. To our knowledge, this is the first case of foveal hypoplasia in a BCM patient and of mild clinical affection in a female carrier caused by the concomitant effect of variants in OPN1LW/OPN1MW and GPR143 genes, thus as the result of the simultaneous action of two independent genetic defects.
Highlights
Blue cone (S cone) monochromatism (BCM) is a rare X-linked congenital cone dysfunction syndrome, caused by mutations in the OPN1LW/OPN1MW gene cluster on theX chromosome
The successful treatment of color blindness in adult monkeys [15], the restoration of cone function in a rat model [16], and other deeper studies on the function of remaining photoreceptor has confirmed the potential effectiveness of gene therapy in BCM [27]
Despite the different molecular genetic mechanisms responsible for the disease, the phenotypes so far reported were relatively homogeneous and mostly characterized by a normal myopic retina with macular retinal pigment epithelial disturbance and atrophy in older patients and significant macular thinning associated with ellipsoid layer disruption at the Spectral-domain optical coherence tomography (SD-OCT) analysis
Summary
Blue cone (S cone) monochromatism (BCM) is a rare X-linked congenital cone dysfunction syndrome, caused by mutations in the OPN1LW/OPN1MW gene cluster on theX chromosome. Blue cone (S cone) monochromatism (BCM) is a rare X-linked congenital cone dysfunction syndrome, caused by mutations in the OPN1LW/OPN1MW gene cluster on the. The cluster contains a single OPN1LW and one or more copies of the OPN1MW gene and controls the expression of the red (L, long wavelength) and green (M, middle wavelength) cone photoreceptor opsins. The genes expressing the opsin for the third cone subtype, S (short wavelength) or blue cones (OPN1SW), and the rod pigment are autosomal and not affected in BCM [1,2,3,4]. Color discrimination is severely impaired from birth and BCM patients typically present reduced visual acuity (6/24 to 6/60), pendular nystagmus, photophobia, and often have a myopic pattern
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