NGS Analysis for Molecular Diagnosis of Retinitis Pigmentosa (RP): Detection of a Novel Variant in PRPH2 Gene

Claudia Strafella, Valerio Caputo, Giulia Pagliaroli, Nicola Iozzo, Giulia Campoli, Stefania Carboni, Cristina Peconi, Rosaria Maria Galota, Stefania Zampatti, Giulietta Minozzi, Giuseppe Novelli, Emiliano Giardina, Raffaella Cascella

Research output: Contribution to journalArticle

Abstract

This work describes the application of NGS for molecular diagnosis of RP in a family with a history of severe hypovision. In particular, the proband received a clinical diagnosis of RP on the basis of medical, instrumental examinations and his family history. The proband was subjected to NGS, utilizing a customized panel including 24 genes associated with RP and other retinal dystrophies. The NGS analysis revealed a novel missense variant (c.668T > A, I223N) in PRPH2 gene, which was investigated by segregation and bioinformatic analysis. The variant is located in the D2 loop domain of PRPH2, which is critical for protein activity. Bioinformatic analysis described the c.668T > A as a likely pathogenic variant. Moreover, a 3D model prediction was performed to better characterize the impact of the variant on the protein, reporting a disruption of the α-helical structures. As a result, the variant protein showed a substantially different conformation with respect to the wild-type PRPH2. The identified variant may therefore affect the oligomerization ability of the D2 loop and, ultimately, hamper PRPH2 proper functioning and localization. In conclusion, PRPH2_c.668T > A provided a molecular explanation of RP symptomatology, highlighting the clinical utility of NGS panels to facilitate genotype-phenotype correlations.

Original languageEnglish
JournalGenes
Volume10
Issue number10
DOIs
Publication statusPublished - Oct 12 2019

Fingerprint

Retinitis Pigmentosa
Computational Biology
Genes
Retinal Dystrophies
Proteins
Genetic Association Studies

Keywords

  • D2 loop domain
  • genotype-phenotype correlation
  • NGS panel
  • PRPH2
  • Retinitis Pigmentosa

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Strafella, C., Caputo, V., Pagliaroli, G., Iozzo, N., Campoli, G., Carboni, S., ... Cascella, R. (2019). NGS Analysis for Molecular Diagnosis of Retinitis Pigmentosa (RP): Detection of a Novel Variant in PRPH2 Gene. Genes, 10(10). https://doi.org/10.3390/genes10100792

NGS Analysis for Molecular Diagnosis of Retinitis Pigmentosa (RP) : Detection of a Novel Variant in PRPH2 Gene. / Strafella, Claudia; Caputo, Valerio; Pagliaroli, Giulia; Iozzo, Nicola; Campoli, Giulia; Carboni, Stefania; Peconi, Cristina; Galota, Rosaria Maria; Zampatti, Stefania; Minozzi, Giulietta; Novelli, Giuseppe; Giardina, Emiliano; Cascella, Raffaella.

In: Genes, Vol. 10, No. 10, 12.10.2019.

Research output: Contribution to journalArticle

Strafella, C, Caputo, V, Pagliaroli, G, Iozzo, N, Campoli, G, Carboni, S, Peconi, C, Galota, RM, Zampatti, S, Minozzi, G, Novelli, G, Giardina, E & Cascella, R 2019, 'NGS Analysis for Molecular Diagnosis of Retinitis Pigmentosa (RP): Detection of a Novel Variant in PRPH2 Gene', Genes, vol. 10, no. 10. https://doi.org/10.3390/genes10100792
Strafella, Claudia ; Caputo, Valerio ; Pagliaroli, Giulia ; Iozzo, Nicola ; Campoli, Giulia ; Carboni, Stefania ; Peconi, Cristina ; Galota, Rosaria Maria ; Zampatti, Stefania ; Minozzi, Giulietta ; Novelli, Giuseppe ; Giardina, Emiliano ; Cascella, Raffaella. / NGS Analysis for Molecular Diagnosis of Retinitis Pigmentosa (RP) : Detection of a Novel Variant in PRPH2 Gene. In: Genes. 2019 ; Vol. 10, No. 10.
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