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Purpose <p>Retinitis Pigmentosa (RP) represents the most common form of inherited retinal dystrophy (IRD), identified by a gradual degeneration of photoreceptors, ultimately resulting in nyctalopia and impaired vision. This study was conducted to screen the rhodopsin and peripherin2 genes for possible pathogenic mutations in north Indian RP patients.</p> Study design <p>We focused on assessing the whole coding region and the intron-exon boundaries of <i>RHO</i> and <i>PRPH2</i> genes in RP patients and control subjects<b>.</b></p> Methods <p>After institutional human ethical clearance and informed consent, a total of seventy-five sporadic cases of RP and one hundred control subjects were enrolled in the current study. Genomic DNA was extracted from the peripheral blood samples of patients and control subjects. PCR-DNA sequencing was performed for coding exons and intron-exon boundaries of <i>RHO</i> and <i>PRPH2</i> genes to identify nucleotide variations in patients and controls. The pathogenicity of identified missense variants was predicted by using six different bioinformatics tools. Structural changes of the protein were analyzed using Garnier–Osguthorpe–Robson, PyMol, ChimeraX, and Molecular Dynamic simulations.</p> Results <p>A total of twenty sequence variants which include 7 missense, 3 synonymous and 10 intronic changes in <i>RHO</i> gene, and fourteen sequence variants which include 9 missense, 4 synonymous and 1 intronic variant in <i>PRPH2</i> gene were identified. Bioinformatic analysis revealed two possible pathogenic missense mutations [p.(E150K) and p.(P347L)] in <i>RHO</i> gene and three possible pathogenic mutations [p.(G31D), p.(D84N), and p.(R220Q)] in <i>PRPH2</i> gene. All five mutations have been previously reported and are documented in publicly available variant databases. Structural alterations were observed in the secondary and tertiary structures of the mutated proteins in cases of pathogenic changes both in rhodopsin and peripherin2 proteins. These structural changes led to protein dysfunction, contributing to disease progression.</p> Conclusion <p>In our study population, we identified five previously reported potentially pathogenic missense variants in the <i>RHO</i> and <i>PRPH2</i> genes, which are associated with retinitis pigmentosa. This data will add to the existing repertoire of disease-causing mutations.</p>

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Genetic and bioinformatic analysis of RHO and PRPH2 variants in north Indian retinitis pigmentosa patients

  • 期刊论文

  • 发表日期：

    2025年8月29日

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  • Aarti Bhardwaj,
  • Jitender Phogat,
  • Manoj Yadav,
  • Anshu Yadav,
  • Vishal Panghal,
  • Mayank Singh,
  • Sapna Sharma,
  • Rakesh Kumar,
  • Mukesh Tanwar

摘要

Purpose

Retinitis Pigmentosa (RP) represents the most common form of inherited retinal dystrophy (IRD), identified by a gradual degeneration of photoreceptors, ultimately resulting in nyctalopia and impaired vision. This study was conducted to screen the rhodopsin and peripherin2 genes for possible pathogenic mutations in north Indian RP patients.

Study design

We focused on assessing the whole coding region and the intron-exon boundaries of RHO and PRPH2 genes in RP patients and control subjects.

Methods

After institutional human ethical clearance and informed consent, a total of seventy-five sporadic cases of RP and one hundred control subjects were enrolled in the current study. Genomic DNA was extracted from the peripheral blood samples of patients and control subjects. PCR-DNA sequencing was performed for coding exons and intron-exon boundaries of RHO and PRPH2 genes to identify nucleotide variations in patients and controls. The pathogenicity of identified missense variants was predicted by using six different bioinformatics tools. Structural changes of the protein were analyzed using Garnier–Osguthorpe–Robson, PyMol, ChimeraX, and Molecular Dynamic simulations.

Results

A total of twenty sequence variants which include 7 missense, 3 synonymous and 10 intronic changes in RHO gene, and fourteen sequence variants which include 9 missense, 4 synonymous and 1 intronic variant in PRPH2 gene were identified. Bioinformatic analysis revealed two possible pathogenic missense mutations [p.(E150K) and p.(P347L)] in RHO gene and three possible pathogenic mutations [p.(G31D), p.(D84N), and p.(R220Q)] in PRPH2 gene. All five mutations have been previously reported and are documented in publicly available variant databases. Structural alterations were observed in the secondary and tertiary structures of the mutated proteins in cases of pathogenic changes both in rhodopsin and peripherin2 proteins. These structural changes led to protein dysfunction, contributing to disease progression.

Conclusion

In our study population, we identified five previously reported potentially pathogenic missense variants in the RHO and PRPH2 genes, which are associated with retinitis pigmentosa. This data will add to the existing repertoire of disease-causing mutations.