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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2021

Open Access 01-12-2021 | Research

Extending the phenotypic spectrum of PRPF8, PRPH2, RP1 and RPGR, and the genotypic spectrum of early-onset severe retinal dystrophy

Authors: Michalis Georgiou, Naser Ali, Elizabeth Yang, Parampal S. Grewal, Tryfon Rotsos, Nikolas Pontikos, Anthony G. Robson, Michel Michaelides

Published in: Orphanet Journal of Rare Diseases | Issue 1/2021

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Abstract

Purpose

To present the detailed retinal phenotype of patients with Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy (LCA/EOSRD) caused by sequence variants in four genes, either not (n = 1) or very rarely (n = 3) previously associated with the disease.

Methods

Retrospective case series of LCA/EOSRD from four pedigrees. Chart review of clinical notes, multimodal retinal imaging, electrophysiology, and molecular genetic testing at a single tertiary referral center (Moorfields Eye Hospital, London, UK).

Results

The mean age of presentation was 3 months of age, with disease onset in the first year of life in all cases. Molecular genetic testing revealed the following disease-causing variants: PRPF8 (heterozygous c.5804G > A), PRPH2 (homozygous c.620_627delinsTA, novel variant), RP1 (homozygous c.4147_4151delGGATT, novel variant) and RPGR (heterozygous c.1894_1897delGACA). PRPF8, PRPH2, and RP1 variants have very rarely been reported, either as unique cases or case reports, with limited clinical data presented. RPGR variants have not previously been associated with LCA/EOSRD. Clinical history and detailed retinal imaging are presented.

Conclusions

The reported cases extend the phenotypic spectrum of PRPF8-, PRPH2-, RP1-, and RPGR-associated disease, and the genotypic spectrum of LCA/EOSRD. The study highlights the importance of retinal and functional phenotyping, and the importance of specific genetic diagnosis to potential future therapy.
Appendix
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Metadata
Title
Extending the phenotypic spectrum of PRPF8, PRPH2, RP1 and RPGR, and the genotypic spectrum of early-onset severe retinal dystrophy
Authors
Michalis Georgiou
Naser Ali
Elizabeth Yang
Parampal S. Grewal
Tryfon Rotsos
Nikolas Pontikos
Anthony G. Robson
Michel Michaelides
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2021
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-021-01759-8

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