Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8456696 | Mutation Research/Reviews in Mutation Research | 2018 | 47 Pages |
Abstract
Choroideremia (CHM) is a rare form of X-linked chorioretinal dystrophy that is caused by mutations in the CHM gene. Mutations in the Rab escort protein-1 (REP-1), an ubiquitously encoded protein of the CHM gene, lead to prenylation and vesicle trafficking deficiency in the protein, resulting in the progressive degeneration of choriocapillaris, retinal pigment epithelium (RPE), and photoreceptors. Despite previous studies concerning this disease, no effective diagnostic tests or established therapeutic interventions currently exist for CHM. In this paper, we reviewed âthe pathogenic âeffects of synonymous hotspot mutation in the CHM gene and the genotypic-phenotypic associations in families with CHM. In addition, we employed a combination of molecular dynamics simulations and principal component analysis to gain insight into the underlying molecular basis of these deleterious and disease-causing hotspot mutation âanalogs. These computer predictions provide strong evidence that the Câ¯>â¯T nonsynonymous hotspot mutations of CHM spectrum contribute to overall RPE retinopathy. These findings increase our understanding of the CHM âpathogenesis, which may potentially define a new approach in developing novel symbiotic strategies for genetic diagnosis and specific treatment of inherited retinal diseases.
Keywords
OMIMGeranylgeranyltransferaseDSSPHotspot mutationChoroideremiaGGTaseNIPDCHMrmsdsHGMDSD-OCTWESRDFONLNGSERGRPEINLelectroretinogramretinal pigment epitheliumOctNoninvasive prenatal diagnosisradial distribution functionsWhole-exome sequencingOptical coherence tomographyVisual acuitySASAMolecular dynamicsRoot Mean Square DeviationsRoot Mean Square FluctuationsSolvent accessible surface areaMolecular dynamics simulationRadius of gyrationouter nuclear layerinner nuclear layerHuman Gene Mutation Database
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Authors
Saber Imani, Iqra Ijaz, Marzieh Dehghan Shasaltaneh, Shangyi Fu, Jingliang Cheng, Junjiang Fu,