Characterization of the Retinal Phenotype Using Multimodal Imaging in Novel Compound Heterozygote Variants of CYP2U1

Ferenc B. Sallo, MD, PhD; Chantal Dysli, MD, PhD; Franz Josef Holzer, MD; Emmanuelle Ranza, MD; Michel Guipponi, MD; Stylianos E. Antonarakis, MD; Francis L. Munier, MD; Alan C. Bird, MD; Daniel F. Schorderet, MD; Beatrice Rossillion, MD; Veronika Vaclavik, MD

Ophthalmology Science (Jan 2025)

Characterization of the Retinal Phenotype Using Multimodal Imaging in Novel Compound Heterozygote Variants of CYP2U1

Ferenc B. Sallo, MD, PhD,
Chantal Dysli, MD, PhD,
Franz Josef Holzer, MD,
Emmanuelle Ranza, MD,
Michel Guipponi, MD,
Stylianos E. Antonarakis, MD,
Francis L. Munier, MD,
Alan C. Bird, MD,
Daniel F. Schorderet, MD,
Beatrice Rossillion, MD,
Veronika Vaclavik, MD

Affiliations

Ferenc B. Sallo, MD, PhD: Oculogenetic Unit, Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland
Chantal Dysli, MD, PhD: Department of Ophthalmology, Inselspital, University of Bern, Bern, Switzerland
Franz Josef Holzer, MD: Department of Neurology, University Hospitals of Geneva, Geneva, Switzerland
Emmanuelle Ranza, MD: Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland
Michel Guipponi, MD: Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland
Stylianos E. Antonarakis, MD: Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland
Francis L. Munier, MD: Oculogenetic Unit, Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland
Alan C. Bird, MD: Department Medical Retina, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom
Daniel F. Schorderet, MD: Institute for Research in Ophthalmology, Sion, Switzerland; Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland; Faculty of Life Sciences, Ecole Polytechnique Federal de Lausanne, Lausanne, Switzerland
Beatrice Rossillion, MD: Vision Rive Droite SA, Grand-Saconnex, Geneva, Switzerland
Veronika Vaclavik, MD: Oculogenetic Unit, Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland; Ophthalmology Department, Hôpital Cantonal de Fribourg, HFR, Fribourg, Switzerland; Correspondence: Veronika Vaclavik, MD, Jules Gonin Eye Hospital, Avenue de France 15, CP 1, 1001 Lausanne, Switzerland.

Journal volume & issue: Vol. 5, no. 1
p. 100618

Abstract

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Purpose: To report the retinal phenotype in 2 patients simulating type 2 macular telangiectasis with new variants in CYP2U1 implicated in hereditary spastic paraplegia type 56 (HSP 56). Design: Cross sectional case series study. Participants: Five members of a non-consanguineous family (parents and 3 male children) were investigated. Methods: All family members underwent a full ophthalmic evaluation and multimodal retinal imaging. Two family members demonstrating retinal anomalies underwent additional OCT angiography, dual wavelength autofluorescence and fluorescence lifetime imaging ophthalmoscopy, kinetic perimetry, fundus-correlated microperimetry, electroretinography, and electro-oculography. Whole-exome sequencing was performed in all 5 family members. Main Outcome Measures: To characterize the retinal phenotype in affected patients with variants in CYP2U1, using multimodal imaging: dual-wavelength autofluorescence, fluorescence lifetime, OCT angiography. Results: The 2 siblings with compound heterozygous novel variants c.452C>T; p.(Pro151Leu), c.943C>T; p.(Gln315Ter) in CYP2U1 demonstrated parafoveal loss of retinal transparency and hyperreflectivity to blue light, redistribution of macular pigment to the parafoveal edge, photoreceptor loss, and fluorescence lifetime imaging ophthalmoscopy anomalies: a pattern compatible with that seen in macular telangiectasia type 2 (MacTel). One had manifest neurological abnormalities since early childhood; the second had no neurological abnormalities. Each parent and the third sibling were heterozygous for 1 variant and were neurologically and ophthalmically normal. Conclusions: These CYP2U1 variants are associated with a retinal phenotype very similar to that otherwise specific for MacTel, suggestive of possible links in the etiology and pathogenesis of these diseases. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Published in Ophthalmology Science

ISSN: 2666-9145 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Ophthalmology
Website: https://www.journals.elsevier.com/ophthalmology-science/

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