Characterisation of the retinal phenotype using multimodal imaging in novel compound heterozygote variants ofCYP2U1

ABSTRACT Purpose To report the retinal phenotype in two patients simulating type 2 macular telangiectasis with new variants in CYP2U1 implicated in Hereditary Spastic Paraplegia type 56 (HSP 56). Methods Five members of a non-consanguineous family (parents and three male children) were investigated. All family members underwent a full ophthalmological 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 five family members. Results The two 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 luteal pigment to the parafoveal edge, photoreceptor loss, FLIO 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 one variant and were neurologically and ophthalmologically normal. Conclusion These CYP2U1 variants are associated with a retinal phenotype very similar to that otherwise specific for MacTel, suggestive of possible links in the aetiology/pathogenesis of these diseases.