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.
NGS Analysis for Molecular Diagnosis of Retinitis Pigmentosa (RP): Detection of a Novel Variant in PRPH2 Gene / C. Strafella, V. Caputo, G. Pagliaroli, N. Iozzo, G. Campoli, S. Carboni, C. Peconi, R. Maria Galota, S. Zampatti, G. Minozzi, G. Novelli, E. Giardina, R. Cascella. - In: GENES. - ISSN 2073-4425. - 10:10(2019 Oct 12), pp. 792.1-792.8.
|Titolo:||NGS Analysis for Molecular Diagnosis of Retinitis Pigmentosa (RP): Detection of a Novel Variant in PRPH2 Gene|
MINOZZI, GIULIETTA [Writing – Review & Editing]
|Parole Chiave:||Retinitis Pigmentosa; NGS panel; PRPH2; D2 loop domain; genotype-phenotype correlation|
|Settore Scientifico Disciplinare:||Settore AGR/17 - Zootecnica Generale e Miglioramento Genetico|
Settore BIO/18 - Genetica
Settore MED/03 - Genetica Medica
|Data di pubblicazione:||12-ott-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/genes10100792|
|Appare nelle tipologie:||01 - Articolo su periodico|