Impairments of Photoreceptor Outer Segments Renewal and Phototransduction Due to a Peripherin Rare Haplotype Variant: Insights from Molecular Modeling
Background: Retinitis pigmentosa punctata albescens (RPA) is a particular form of retinitis pigmentosa characterized by childhood onset night blindness and areas of peripheral retinal atrophy. We investigated the genetic cause of RPA in a family consisting of two affected Egyptian brothers with heal...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/7/3484 |
| Summary: | Background: Retinitis pigmentosa punctata albescens (RPA) is a particular form of retinitis pigmentosa characterized by childhood onset night blindness and areas of peripheral retinal atrophy. We investigated the genetic cause of RPA in a family consisting of two affected Egyptian brothers with healthy consanguineous parents. Methods: Mutational analysis of four RPA causative genes was realized by Sanger sequencing on both probands, and detected variants were subsequently genotyped in their parents. Afterwards, found variants were deeply, statistically, and in silico characterized to determine their possible effects and association with RPA. Results: Both brothers carry three missense <i>PRPH2</i> variants in a homozygous condition (c.910C > A, c.929G > A, and c.1013A > C) and two promoter variants in <i>RHO</i> (c.-26A > G) and <i>RLBP1</i> (c.-70G > A) genes, respectively. Haplotype analyses highlighted a <i>PRPH2</i> rare haplotype variant (GAG), determining a possible alteration of <i>PRPH2</i> binding with melanoregulin and other outer segment proteins, followed by photoreceptor outer segment instability. Furthermore, an altered balance of transcription factor binding sites, due to the presence of <i>RHO</i> and <i>RLBP1</i> promoter variants, might determine a comprehensive downregulation of both genes, possibly altering the <i>PRPH2</i> shared visual-related pathway. Conclusions: Despite several limitations, the study might be a relevant step towards detection of novel scenarios in RPA etiopathogenesis. |
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| ISSN: | 1661-6596 1422-0067 |