Ghiam Sean, Zukerman Ryan, Brzozowski Morgan, Alabek Michelle, Hagan Richard, Beryozkin Avigail, Sahel José-Alain, Rosin Boris
Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, PA, USA.
Institut De La Vision, INSERM, CNRS, Sorbonne Université, Paris, France.
Case Rep Ophthalmol. 2025 May 20;16(1):416-425. doi: 10.1159/000546220. eCollection 2025 Jan-Dec.
The purpose of this report was to highlight the clinical phenotype and imaging findings in a patient with an exclusively macular phenotype of non-syndromic -related disease and to provide clinical evidence for pathogenicity reclassification of a variant of uncertain significance c.291G>C (p.Trp97Cys).
A 47-year-old male with progressive vision loss exhibited symptoms indicative of maculopathy. These included decreased central vision, visual distortions, photophobia, poor depth perception, glare, impaired dark/light adaptation, difficulty reading, depressed multifocal ERG responses, and central ellipsoid dropout on SD-OCT. Evaluation included genetic testing, segregation analysis, and a complete ophthalmic examination, including slit-lamp exam, dilated fundus exam, FAF, SD-OCT, ERG, and Humphrey 24-2 visual fields. A 351 gene retinal dystrophy panel revealed two variants in , including one pathogenic variant (c.1006G>C, p.Glu336Gln) and one likely pathogenic variant (c.291G>C, p.Trp97Cys), confirmed to be in trans via segregation testing.
This case underscores the importance of genetic testing in confirming variant inheritance and describes the clinical phenotype associated with MFSD8 c.291G>C (p.Trp97Cys). The variant contributes to a pathological non-syndromic phenotype when in trans with a pathogenic variant. Given the syndromic variants of , patients with this specific variant in the homozygous or compound heterozygous state should be closely monitored for clinical manifestations associated with this condition. Genetic counseling should be recommended for affected individuals and their close relatives to provide informed guidance regarding prognosis, reproductive risks, and available support resources.
本报告的目的是突出一名患有非综合征相关疾病单纯黄斑表型患者的临床表型和影像学表现，并为意义未明的变异体c.291G>C（p.Trp97Cys）的致病性重新分类提供临床证据。
一名47岁男性，视力进行性下降，表现出黄斑病变的症状。这些症状包括中心视力下降、视觉变形、畏光、深度感知差、眩光、暗/光适应受损、阅读困难、多焦视网膜电图反应降低以及频域光学相干断层扫描（SD-OCT）显示的中心椭圆体缺失。评估包括基因检测、分离分析以及全面的眼科检查，包括裂隙灯检查、散瞳眼底检查、自发荧光（FAF）、SD-OCT、视网膜电图（ERG）和 Humphrey 24-2视野检查。一项351基因视网膜营养不良检测 panel 显示两个变异体，包括一个致病变异体（c.1006G>C，p.Glu336Gln）和一个可能的致病变异体（c.291G>C，p.Trp97Cys），通过分离检测证实为反式。
本病例强调了基因检测在确认变异体遗传方面的重要性，并描述了与MFSD8 c.291G>C（p.Trp97Cys）相关的临床表型。该变异体与一个致病变异体反式时会导致病理性非综合征表型。鉴于[相关基因]的综合征变异体，纯合或复合杂合状态下具有这种特定变异体的患者应密切监测与该疾病相关的临床表现。应建议受影响个体及其近亲进行遗传咨询，以提供关于预后、生殖风险和可用支持资源的知情指导。
