Journal Article

PRPH2-Related Retinal Dystrophies: Mutational Spectrum in 103 Families from a Spanish Cohort

Perea-Romero, Irene, Blanco-Kelly, Fiona, Avila-Fernandez, Almudena, Trujillo-Tiebas, María José, Mahillo, Ignacio, Minguez, Pablo, Carreño, Ester, Sánchez-Barbero, Ana Isabel, Martin-Gutierrez, María Pilar, Irigoyen, Cristina, Swafiri, Saoud T., Zurita, Olga, Ayuso, Carmen, García-Sandoval, Blanca, Lopez-Grondona, Fermina, Fernandez-San Jose, Patricia, Riveiro-Alvarez, Rosa, Jimenez-Rolando, Belen, Rodriguez-Peña, Lidya, Rodilla, Cristina, Fernández-Caballero, Lidia, Martín-Merida, Inmaculada, Del Pozo-Valero, Marta, Corton, Marta

2024

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Disease / DNA Mutational Analysis / Genes / Genotype & phenotype / Haplotypes / Humans / Mutation / Mutation, Missense / Pedigree / Phenotype / Proteins / Retinal Dystrophies - genetics / Retinitis Pigmentosa - genetics