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

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

doi:10.1016/j.xops.2024.100618

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

Ophthalmol Sci. 2024 Sep 11;5(1):100618. doi: 10.1016/j.xops.2024.100618. eCollection 2025 Jan-Feb.

Authors

Affiliations

¹ Oculogenetic Unit, Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland.
² Department of Ophthalmology, Inselspital, University of Bern, Bern, Switzerland.
³ Department of Neurology, University Hospitals of Geneva, Geneva, Switzerland.
⁴ Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
⁵ Department Medical Retina, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom.
⁶ Institute for Research in Ophthalmology, Sion, Switzerland.
⁷ Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland.
⁸ Faculty of Life Sciences, Ecole Polytechnique Federal de Lausanne, Lausanne, Switzerland.
⁹ Vision Rive Droite SA, Grand-Saconnex, Geneva, Switzerland.
¹⁰ Ophthalmology Department, Hôpital Cantonal de Fribourg, HFR, Fribourg, Switzerland.

Abstract

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 disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Keywords: CYP2U1; Hereditary Spastic Paraplegia type 56; MacTel; Maculopathy; Multimodal imaging.