Blue Cone Monochromatism with Foveal Hypoplasia Caused by the Concomitant Effect of Variants in <i>OPN1LW/OPN1MW</i> and <i>GPR143</i> Genes

• Main Authors: Giancarlo Iarossi, Andrea Maria Coppè, Chiara Passarelli, Paolo Enrico Maltese, Lorenzo Sinibaldi, Alessandro Cappelli, Sarah Cetola, Antonio Novelli, Luca Buzzonetti
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: International Journal of Molecular Sciences
• Subjects: blue cone monochromatism; X-linked inheritance; foveal hypoplasia; <i>OPN1LW/OPN1MW</i> gene cluster
• Online Access: https://www.mdpi.com/1422-0067/22/16/8617

Blue cone monochromatism (BCM) is an X-linked recessive cone dysfunction disorder caused by mutations in the <i>OPN1LW/OPN1MW</i> 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 <i>OPN1LW</i> 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 <i>OPN1LW</i> gene and the common missense mutation c.607T > C (p.Cys203Arg) in the <i>OPN1MW</i> gene. In addition, we discovered the c.768-2_769delAGTT splicing variant in the <i>GPR143</i> 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 <i>OPN1LW/OPN1MW</i> and <i>GPR143</i> genes, thus as the result of the simultaneous action of two independent genetic defects.