Dataset Information

Retinitis Punctata Albescens and RLBP1-Allied Phenotypes: Phenotype-Genotype Correlation and Natural History in the Aim of Gene Therapy.

ABSTRACT:

Purpose

To identify relevant criteria for gene therapy based on clinical and genetic characteristics of rod-cone dystrophy associated with RLBP1 pathogenic variants in a large cohort comprising children and adults.

Design

Retrospective cohort study.

Participants

Patients with pathogenic variants in RLBP1 registered in a single French reference center specialized in inherited retinal dystrophies.

Methods

Clinical, multimodal imaging, and genetic findings were reviewed.

Main outcome measures

Age of onset; visual acuity; ellipsoid line length; nasal, temporal, and foveal retinal thickness; and pathogenic variants and related phenotypes, including Newfoundland rod-cone and Bothnia dystrophies (NFRCDs), were reappraised.

Results

Twenty-one patients (15 families) were included. The most frequent form was NFRCD with 12 patients (8 families) homozygous for the recurrent deletion of exons 7 through 9 in RLBP1 and 5 patients (4 families) with biallelic protein-truncating variants (2 novel: p.Gln16∗ and p.Tyr251∗). A novel combination of the p.Arg234Trp Bothnia variant with a nonsense variant in trans led to Bothnia dystrophy in 2 sisters. One proband carrying the p.Met266Lys Bothnia variant and in trans p.Arg121Trp and a second, with the p.Arg9Cys and p.Tyr111∗ combination, both demonstrated mild retinitis punctata albescens. Independently of genotype, all patients showed a visual acuity of worse than 20/200, an ellipsoid line width of less than 1000 μm, and a mean foveal thickness of less than 130 to 150 μm, with loss of both the interdigitation and ellipsoid lines.

Conclusions

The eligibility for RLBP1 gene therapy first should be determined according to the biallelic variant combination using a robust classification as proposed herein. An ellipsoid line width of more than 1200 μm and a central thickness of more than 130 to 150 μm with detectable ellipsoid and interdigitation lines should be 2 prerequisite imaging indicators for gene therapy.

SUBMITTER: Bocquet B

PROVIDER: S-EPMC9559097 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Retinitis Punctata Albescens and <i>RLBP1</i>-Allied Phenotypes: Phenotype-Genotype Correlation and Natural History in the Aim of Gene Therapy.

Bocquet Béatrice B El Alami Trebki Hicham H Roux Anne Françoise AF Labesse Gilles G Brabet Philippe P Arndt Carl C Zanlonghi Xavier X Defoort-Dhellemmes Sabine S Hamroun Dalil D Boulicot-Séguin Céline C Lequeux Léopoldine L Picot Marie Christine MC Huguet Hélèna H Audo Isabelle I Dhaenens Claire Marie CM Kalatzis Vasiliki V Meunier Isabelle I

Ophthalmology science 20210817 3

<h4>Purpose</h4>To identify relevant criteria for gene therapy based on clinical and genetic characteristics of rod-cone dystrophy associated with <i>RLBP1</i> pathogenic variants in a large cohort comprising children and adults.<h4>Design</h4>Retrospective cohort study.<h4>Participants</h4>Patients with pathogenic variants in <i>RLBP1</i> registered in a single French reference center specialized in inherited retinal dystrophies.<h4>Methods</h4>Clinical, multimodal imaging, and genetic findings ...[more]

PMID: 36247817

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