The First Homozygote Mutation c.499G>T (Asp167Tyr) in the <i>RPE65</i> Gene Encoding Retinoid <i>Isomerohydrolase</i> Causing Retinal Dystrophy
RPE65, an abundant membrane-associated protein present in the retinal pigment epithelium (RPE), is a vital retinoid isomerase necessary for regenerating 11-<i>cis</i>-retinaldehyde from <i>all-trans</i> retinol in the visual cycle. In patients with inherited retinal dystrophy...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Current Issues in Molecular Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1467-3045/44/12/436 |
| Summary: | RPE65, an abundant membrane-associated protein present in the retinal pigment epithelium (RPE), is a vital retinoid isomerase necessary for regenerating 11-<i>cis</i>-retinaldehyde from <i>all-trans</i> retinol in the visual cycle. In patients with inherited retinal dystrophy (IRD), precise genetic diagnosis is an indispensable approach as it is required to establish eligibility for the genetic treatment of <i>RPE65</i>-associated IRDs. This case report aims to report the specific phenotype–genotype correlation of the first patient with a homozygous missense variant <i>RPE65</i> c.499G>T, p. (Asp167Tyr). We report a case of a 66-year-old male who demonstrated a unique phenotype manifesting less severe functional vision deterioration in childhood and adolescence, and extensive nummular pigment clusters. The underlying causes of the differences in the typical bone spicule and atypical nummular pigment clumping are unknown, but suggest that the variant itself influenced the rate of photoreceptor death. Functional studies are needed to define whether the substitution of aspartate impairs the folding of the tertiary RPE65 structure only and does not lead to the complete abolishment of chromophore production, thus explaining the less severe phenotype in adolescence. |
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| ISSN: | 1467-3037 1467-3045 |