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Open AccessArticle

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

1
Molecular Genetics Laboratory UILDM, Santa Lucia Foundation, 00179 Rome, Italy
2
Department of Biomedicine and Prevention, Tor Vergata University, 00133 Rome, Italy
3
Organi di Senso Department, University “la Sapienza”, 00161 Rome, Italy
4
Department of Veterinary Medicine, University of Milan, 20122 Milan, Italy
5
Neuromed IRCSS, 86077 Pozzilli, Italy
6
Department of Biomedical Sciences, Catholic University Our Lady of Good Counsel, 1000 Tirana, Albania
*
Author to whom correspondence should be addressed.
These authors equally contributed to the work.
Genes 2019, 10(10), 792; https://doi.org/10.3390/genes10100792 (registering DOI)
Received: 18 September 2019 / Revised: 4 October 2019 / Accepted: 11 October 2019 / Published: 12 October 2019
(This article belongs to the Special Issue Recent Advances in Inherited Eye Disease)
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. View Full-Text
Keywords: Retinitis Pigmentosa; NGS panel; PRPH2; D2 loop domain; genotype-phenotype correlation Retinitis Pigmentosa; NGS panel; PRPH2; D2 loop domain; genotype-phenotype correlation
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Strafella, C.; Caputo, V.; Pagliaroli, G.; Iozzo, N.; Campoli, G.; Carboni, S.; Peconi, C.; Galota, R.M.; Zampatti, S.; Minozzi, G.; Novelli, G.; Giardina, E.; Cascella, R. NGS Analysis for Molecular Diagnosis of Retinitis Pigmentosa (RP): Detection of a Novel Variant in PRPH2 Gene. Genes 2019, 10, 792.

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