학술논문
PRPH2 -Related Retinal Dystrophies: Mutational Spectrum in 103 Families from a Spanish Cohort.
Document Type
Article
Author
Fernández-Caballero, Lidia; Martín-Merida, Inmaculada; Blanco-Kelly, Fiona; Avila-Fernandez, Almudena; Carreño, Ester; Fernandez-San Jose, Patricia; Irigoyen, Cristina; Jimenez-Rolando, Belen; Lopez-Grondona, Fermina; Mahillo, Ignacio; Martin-Gutierrez, María Pilar; Minguez, Pablo; Perea-Romero, Irene; Del Pozo-Valero, Marta; Riveiro-Alvarez, Rosa; Rodilla, Cristina; Rodriguez-Peña, Lidya; Sánchez-Barbero, Ana Isabel; Swafiri, Saoud T.; Trujillo-Tiebas, María José
Source
Subject
*RETINAL degeneration
*RETINITIS pigmentosa
*PHENOTYPIC plasticity
*SINGLE nucleotide polymorphisms
*MISSENSE mutation
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Language
ISSN
1661-6596
Abstract
PRPH2, one of the most frequently inherited retinal dystrophy (IRD)-causing genes, implies a high phenotypic variability. This study aims to analyze the PRPH2 mutational spectrum in one of the largest cohorts worldwide, and to describe novel pathogenic variants and genotype–phenotype correlations. A study of 220 patients from 103 families recruited from a database of 5000 families. A molecular diagnosis was performed using classical molecular approaches and next-generation sequencing. Common haplotypes were ascertained by analyzing single-nucleotide polymorphisms. We identified 56 variants, including 11 novel variants. Most of them were missense variants (64%) and were located in the D2-loop protein domain (77%). The most frequently occurring variants were p.Gly167Ser, p.Gly208Asp and p.Pro221_Cys222del. Haplotype analysis revealed a shared region in families carrying p.Leu41Pro or p.Pro221_Cys222del. Patients with retinitis pigmentosa presented an earlier disease onset. We describe the largest cohort of IRD families associated with PRPH2 from a single center. Most variants were located in the D2-loop domain, highlighting its importance in interacting with other proteins. Our work suggests a likely founder effect for the variants p.Leu41Pro and p.Pro221_Cys222del in our Spanish cohort. Phenotypes with a primary rod alteration presented more severe affectation. Finally, the high phenotypic variability in PRPH2 hinders the possibility of drawing genotype–phenotype correlations. [ABSTRACT FROM AUTHOR]