Eye Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE.
Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
Ophthalmic Genet. 2023 Dec;44(6):595-597. doi: 10.1080/13816810.2023.2175224. Epub 2023 Feb 10.
Bialleic pathogenic variants are typically associated with severe Leber congenital amaurosis (non-recordable electroretinography [ERG]) and less commonly with cone-rod dystrophy. This report highlights isolated cone dysfunction as an alternative -related presenting phenotype.
Retrospective case series.
Four individuals (two sibships from two unrelated families) had low vision, nystagmus, photophobia, and a grossly normal retinal appearance since soon after birth. ERG confirmed non-recordable photopic function with normal scotopic function. Genetic testing revealed affected members from the two families to harbor two different homozygous variants (Family 1: c.3565C>T; p.Arg1189*; Family 2: c.2711_2741delinsATATTAG; p.Gly904_Lys914delinsAspIIeArg). Follow-up for Family 1 revealed deterioration of pan-retinal function (non-recordable ERGs by 11 and 7 years old) and thus a final diagnosis of cone-rod dystrophy. Follow-up for Family 2 showed stable retinal function (normal ERG scotopic tracings maintained at 12 and 21 years old) and thus a diagnosis of isolated cone dysfunction.
Isolated cone dysfunction that progresses to pan-retinal dysfunction or remains relatively stationary is an alternative phenotype related to biallelic pathogenic variants.
双等位致病性变异通常与严重的莱伯先天性黑蒙（无法记录的视网膜电图 [ERG]）相关，较少与 Cone-Rod 营养不良相关。本报告强调了孤立的 Cone 功能障碍是一种相关的表现型。
回顾性病例系列。
四名个体（来自两个无关家庭的两个同胞）自出生后不久就出现了低视力、眼球震颤、畏光和明显正常的视网膜外观。ERG 证实光感受器功能无法记录，而暗适应功能正常。遗传检测显示，来自两个家庭的受影响成员携带两种不同的纯合变异（家族 1：c.3565C>T；p.Arg1189*；家族 2：c.2711_2741delinsATATTAG；p.Gly904_Lys914delinsAspIIeArg）。对家族 1 的随访显示全视网膜功能恶化（11 岁和 7 岁时无法记录 ERG），最终诊断为 Cone-Rod 营养不良。对家族 2 的随访显示视网膜功能稳定（12 岁和 21 岁时正常的 ERG 暗适应记录保持不变），因此诊断为孤立的 Cone 功能障碍。
进展为全视网膜功能障碍或保持相对稳定的孤立的 Cone 功能障碍是与双等位致病性变异相关的另一种表型。
