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Longitudinal Clinical Follow-up and Genetic Spectrum of Patients With Rod-Cone Dystrophy Associated With Mutations in PDE6A and PDE6B.

Abstract：

Importance:A precise phenotypic characterization of retinal dystrophies is needed for disease modeling as a basis for future therapeutic interventions. Objective:To compare genotype, phenotype, and structural changes in patients with rod-cone dystrophy (RCD) associated with mutations in PDE6A or PDE6B. Design, Setting, and Participants:In a retrospective cohort study conducted in Paris, France, from January 2007 to September 2017, 54 patients from a cohort of 1095 index patients with RCD underwent clinical examination, including personal and familial history, best-corrected visual acuity (BCVA), color vision, slitlamp examination, full-field electroretinography, kinetic visual fields (VFs), retinophotography, optical coherence tomography, near-infrared fundus autofluorescence, and short-wavelength fundus autofluorescence imaging. Genotyping was performed using microarray analysis, targeted next-generation sequencing, and Sanger sequencing validation with familial segregation when possible. Data were analyzed from September 1, 2017, to February 1, 2018. Clinical variables were subsequently analyzed in 2018. Main Outcomes and Measures:Phenotype and genotype comparison of patients carrying mutations in PDE6A or PDE6B. Results:Of the 54 patients included in the study, 19 patients of 17 families (11 women [58%]; mean [SD] age at diagnosis, 14.83 [10.63] years) carried pathogenic mutations in PDE6A, and 35 patients of 26 families (17 women [49%]; mean [SD] age at diagnosis, 21.10 [11.56] years) had mutations in PDE6B, accounting for prevalences of 1.6% and 2.4%, respectively. Among 49 identified genetic variants, 14 in PDE6A and 15 in PDE6B were novel. Overall, phenotypic analysis revealed no substantial differences between the 2 groups except for night blindness as a presenting symptom that was noted to be more prevalent in the PDE6A than PDE6B group (80% vs 37%, respectively; P = .005). The mean binocular BCVA and VF decrease over time (measured as mean individual slopes coefficients) was comparable between patients with PDE6A and PDE6B mutations: 0.04 (0.12) vs 0.02 (0.05) for BCVA (P = .89) and 14.33 (7.12) vs 13.27 (6.77) for VF (P = .48). Conclusions and Relevance:Mutations in PDE6A and PDE6B accounted for 1.6% and 2.4%, respectively, in a cohort of French patients with RCD. The functional and structural findings reported may constitute the basis of disease modeling that might be used for better prognostic estimation and candidate selection for photoreceptor therapeutic rescue.

journal_name

JAMA Ophthalmol

journal_title

JAMA ophthalmology

authors

Khateb S,Nassisi M,Bujakowska KM,Méjécase C,Condroyer C,Antonio A,Foussard M,Démontant V,Mohand-Saïd S,Sahel JA,Zeitz C,Audo I

doi

10.1001/jamaophthalmol.2018.6367

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

669-679

issue

eissn

2168-6165

issn

2168-6173

pii

2731478

journal_volume

137

pub_type

杂志文章

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Longitudinal Clinical Follow-up and Genetic Spectrum of Patients With Rod-Cone Dystrophy Associated With Mutations in PDE6A and PDE6B.