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 language | English |
|---|---|
| Journal | Genes |
| Volume | 10 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 12 2019 |
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Keywords
- D2 loop domain
- genotype-phenotype correlation
- NGS panel
- PRPH2
- Retinitis Pigmentosa
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
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 journal › Article
}
TY - JOUR
T1 - NGS Analysis for Molecular Diagnosis of Retinitis Pigmentosa (RP)
T2 - Detection of a Novel Variant in PRPH2 Gene
AU - Strafella, Claudia
AU - Caputo, Valerio
AU - Pagliaroli, Giulia
AU - Iozzo, Nicola
AU - Campoli, Giulia
AU - Carboni, Stefania
AU - Peconi, Cristina
AU - Galota, Rosaria Maria
AU - Zampatti, Stefania
AU - Minozzi, Giulietta
AU - Novelli, Giuseppe
AU - Giardina, Emiliano
AU - Cascella, Raffaella
PY - 2019/10/12
Y1 - 2019/10/12
N2 - 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.
AB - 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.
KW - D2 loop domain
KW - genotype-phenotype correlation
KW - NGS panel
KW - PRPH2
KW - Retinitis Pigmentosa
UR - http://www.scopus.com/inward/record.url?scp=85073437725&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073437725&partnerID=8YFLogxK
U2 - 10.3390/genes10100792
DO - 10.3390/genes10100792
M3 - Article
C2 - 31614793
AN - SCOPUS:85073437725
VL - 10
JO - Genes
JF - Genes
SN - 2073-4425
IS - 10
ER -