Sallo, Ferenc BFerenc BSalloDysli, ChantalChantalDysliHolzer, Franz JosefFranz JosefHolzerRanza, EmmanuelleEmmanuelleRanzaGuipponi, MichelMichelGuipponiAntonarakis, Stylianos EStylianos EAntonarakisMunier, Francis LFrancis LMunierBird, Alan CAlan CBirdSchorderet, Daniel FDaniel FSchorderetRossillion, BeatriceBeatriceRossillionVaclavik, VeronikaVeronikaVaclavik2024-12-132024-12-132025https://boris-portal.unibe.ch/handle/20.500.12422/191345Purpose 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.enCYP2U1Hereditary Spastic Paraplegia type 56MacTelMaculopathyMultimodal imaging600 - Technology::610 - Medicine & healtharticle10.48620/774813960587310.1016/j.xops.2024.100618