利用多模态成像确定 CYP2U1 新型复合杂合子变异体视网膜表型的特征

IF 3.2 Q1 OPHTHALMOLOGY Ophthalmology science Pub Date : 2024-09-11 DOI:10.1016/j.xops.2024.100618

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

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引用次数: 0

摘要

目的报告 2 例类似 2 型黄斑毛细血管扩张症的患者的视网膜表型，这些患者体内的 CYP2U1 存在新变异，与遗传性痉挛性截瘫 56 型（HSP 56）有关。方法所有家庭成员都接受了全面的眼科评估和多模式视网膜成像。两个视网膜异常的家族成员接受了额外的 OCT 血管造影、双波长自发荧光和荧光寿命成像眼底镜检查、动力性视力测定、眼底相关显微视力测定、视网膜电图和眼底电图检查。主要结果通过多模态成像：双波长自发荧光、荧光寿命、OCT 血管造影，描述 CYP2U1 变异患者的视网膜表型。C>T;p.(Gln315Ter)的两个兄弟姐妹的视网膜视网膜透明度下降，对蓝光有高反射性，黄斑色素重新分布到视网膜视网膜边缘，感光器缺失，荧光寿命成像眼底镜检查异常：与黄斑毛细血管扩张症 2 型（MacTel）的模式一致。其中一人从幼年起就有明显的神经系统异常，而第二个兄弟姐妹则没有神经系统异常。结论这些CYP2U1变体与MacTel的视网膜表型非常相似，提示这些疾病的病因和发病机制可能存在联系。

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

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.