Supplementary Material for: Detailed Phenotype Supports Pathogenicity of Hypomorphic Variant in ABCC6-Associated Pattern Dystrophy

INTRODUCTION: We report a case of pseudoxanthoma elasticum (PXE) with an atypical phenotype likely related to a hypomorphic variant in ABCC6.
CASE PRESENTATION: A 66-year-old Caucasian female with a history of a maculopathy interpreted as either age-related macular degeneration (AMD) or a pattern dystrophy underwent a detailed ophthalmic evaluation. Visual acuities were 20/25, OD, and 20/20, OS. Spectral domain optical coherence and fluorescein angiography demonstrated outer retinal disruptions and breaks in retinal pigment epithelium/Bruch’s membrane (RPE/BrM) bilaterally, consistent with angioid streaks. A large area of hypo- and hyperautofluorescence extending from the central retina into the peripapillary retina was documented with short-wavelength excitation autofluorescence. The area of hypoautofluorescence, which was much larger on near-infrared excitation, spared the temporal retina. Two-color dark-adapted perimetries documented severe rod sensitivity losses and less severe cone sensitivity abnormalities co-localizing with the RPE abnormalities. No obvious skin findings were observed and initial dermatologic biopsy was negative. Gene screening identified a pathogenic ABCC6 gene variant c.1552 C>T and a previously reported variant of uncertain significance c.1171A>G. A second dermatologic biopsy demonstrated positive findings consistent with pseudoxanthoma elasticum.
CONCLUSION: Although this patient had minimal skin findings, this patient had characteristic structural and functional abnormalities of a pattern dystrophy with angioid streaks and histologic evidence of PXE, suggesting compound heterozygous variants involving the hypomorphic ABCC6 c.1171A>G variant. These findings support the pathogenic role of both variants.

引言：本报告探讨了一例伪弹性假黄瘤（PXE）的病例，其典型症状可能与ABCC6基因的杂合性变异有关。
病例介绍：一位66岁的白人女性，既往病史包括被诊断为年龄相关性黄斑变性（AMD）或图式性萎缩的脉络膜视网膜病变，接受了详细的眼科评估。视力为OD 20/25，OS 20/20。光谱域光学相干断层扫描和荧光素眼底血管造影显示双眼视网膜外层出现中断和视网膜色素上皮/布鲁奇膜（RPE/BrM）破裂，符合血管翳条纹的特征。使用短波激发的自荧光检查记录了一个从黄斑中心扩展至视盘周围视网膜的大面积低荧光和高荧光区域。近红外激发下的低荧光区域较大，且未侵犯颞侧视网膜。双色暗适应视野检查显示严重的视杆细胞敏感性丧失和较轻的视锥细胞敏感性异常，这些异常与RPE病变共存。未观察到明显的皮肤病变，初步皮肤活检结果为阴性。基因筛查发现了一种致病性ABCC6基因变异c.1552 C>T和一种报道过的意义不明的变异c.1171A>G。第二次皮肤活检显示阳性结果，与伪弹性假黄瘤相符。
结论：尽管该患者皮肤病变不明显，但其表现出典型的图式性萎缩结构性和功能性异常，包括血管翳条纹和PXE的病理学证据，提示涉及杂合性ABCC6 c.1171A>G变异的复合杂合性变异。这些发现支持了两种变异致病性的作用。